Updated on 2026/03/19

写真a

 
HIRATA Dai
 
Organization
Academic Assembly Institute of Science and Technology NOUGAKU KEIRETSU Professor
Faculty of Agriculture Department of Agriculture Professor
Title
Professor
Homepage
https://sake.niigata-u.ac.jp/
External link

Degree

  • 博士（工学） ( 1992.11   広島大学 )

Research Interests

  • Zymurgy for Healthy Aging

  • Yeast

  • Sakeology

  • Molecular Biology

Research Areas

  • Life Science / Molecular biology

Research History (researchmap)

  • Niigata University   Sakeology Center   Professor

    2020.2

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  • Niigata University   Faculty of Agriculture   Professor

    2020.1

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  • 朝日酒造株式会社   取締役（非常勤）

    2019.12

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  • 日本酒造協同組合連合会   理事 原料委員

    2016.12

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  • 新潟県酒造組合   副会長

    2015.7

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  • Hiroshima University

    2014.6

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  • 朝日酒造株式会社   部長(201406-1901), 日本酒研究センター長(1902-12), 取締役(1412-1912)

    2014.6 - 2019.12

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  • 独立行政法人酒類総合研究所研究開発評価委員会   評価委員

    2008.4

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  • Hiroshima University   Professor

    2004.4 - 2014.5

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  • 科学技術振興事業団PRESTO「素過程と連携」領域   研究員

    1998.9 - 2001.8

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  • Hiroshima University   Associate Professor (as old post name)

    1997.4 - 2004.3

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  • Imperial Cancer Research Fund   Visiting Scientist

    1994.7 - 1995.10

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  • Hiroshima University   Research Assistant

    1992.4 - 1997.3

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  • 新潟県醸造試験場

    1987.4 - 1992.3

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Research History

  • Niigata University   Sakeology Center   Professor

    2020.2

  • Niigata University   Faculty of Agriculture Department of Agriculture   Professor

    2020.1

Education

  • Hiroshima University   Graduate School, Division of Engineering

    1985.4 - 1987.3

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    Country： Japan

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  • Hiroshima University   Graduate School, Division of Engineering

    - 1987

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  • Hiroshima University   工学研究科   工業化学

    - 1987

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    Country： Japan

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  • Hiroshima University   Faculty of Engineering   醗酵工学

    1981.4 - 1985.3

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    Country： Japan

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  • Hiroshima University   Faculty of Engineering

    - 1985

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Professional Memberships

  • 日本分子生物学会

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  • 酵母遺伝学集談会（現：酵母遺伝学フォーラム）

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  • 日本農芸化学会

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Committee Memberships

  • 酒米研究会   会長  

    2011.5   

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    Committee type：Other

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Papers

  • Calcineurin ensures a link between the DNA replication checkpoint and microtubule-dependent polarized growth. Reviewed

    Kume Kazunori, Koyano Takayuki, Kanai Muneyoshi, Toda Takashi, Hirata Dai

    Calcineurin ensures a link between the DNA replication checkpoint and microtubule-dependent polarized growth.   13 ( 3 )   234 - U357   2011

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    Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

    :Microtubules are central to eukaryotic cell morphogenesis. Microtubule plus-end tracking proteins (+TIPs) transport polarity factors to the cell cortex, thereby playing a key role in both microtubule dynamics and cell polarity. However, the signalling pathway linking +TIPs to cell polarity control remains elusive. Here we show that the fission yeast checkpoint kinase Cds1 (Chk2 homologue) delays the transition of growth polarity from monopolar to bipolar (termed NETO; new-end take-off). The +TIPs CLIP170 homologue Tip1 and kinesin Tea2 are responsible for this delay, which is accompanied by a reduction in microtubule dynamics at the cell tip. Remarkably, microtubule stabilization occurs asymmetrically, prominently at the non-growing cell end, which induces abnormal accumulation of the polarity factor Tea1. Importantly, NETO delay requires activation of calcineurin, which is carried out by Cds1, resulting in Tip1 dephosphorylation. Thus, our study establishes a critical link between calcineurin and checkpoint-dependent cell morphogenesis.

    DOI： 10.1038/ncb2166

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  • Fission yeast MO25 protein is localized at SPB and septum and is essential for cell morphogenesis Reviewed

    Kanai, M, Kume, K, Miyahara, K, Sakai, K, Nakamura, K, Leonhard, K, Wiley, DJ, Verde, F, Toda, T, Hirata, D

    EMBO JOURNAL   24 ( 17 )   3012 - 3025   2005.9

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    Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

    Cell morphogenesis is of fundamental significance in all eukaryotes for development, differentiation, and cell proliferation. In fission yeast, Drosophila Furry-like Mor2 plays an essential role in cell morphogenesis in concert with the NDR/Tricornered kinase Orb6. Mutations of these genes result in the loss of cell polarity. Here we show that the conserved proteins, MO25-like Pmo25, GC kinase Nak1, Mor2, and Orb6, constitute a morphogenesis network that is important for polarity control and cell separation. Intriguingly, Pmo25 was localized at the mitotic spindle pole bodies (SPBs) and then underwent translocation to the dividing medial region upon cytokinesis. Pmo25 formed a complex with Nak1 and was required for both the localization and kinase activity of Nak1. Pmo25 and Nak1 in turn were essential for Orb6 kinase activity. Further, the Pmo25 localization at the SPBs and the Nak1-Orb6 kinase activities during interphase were under the control of the Cdc7 and Sid1 kinases in the septation initiation network (SIN), suggesting a functional linkage between SIN and the network for cell morphogenesis/ separation following cytokinesis.

    DOI： 10.1038/sj.emboj.7600782

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  • Combinatory breeding of sake yeast strains with mutations that enhance Ginjo aroma production. International journal

    Yifeng Gong, Norapat Klinkaewboonwong, Risa Hayashi, Yan Zhou, Ikuhisa Nishida, Rei Saito, Tetsuya Goshima, Tomoyuki Nishi, Daisuke Watanabe, Dai Hirata, Takeshi Akao, Yoshikazu Ohya

    Bioscience, biotechnology, and biochemistry   89 ( 6 )   910 - 917   2025.5

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    Language：English   Publishing type：Research paper (scientific journal)  

    Isoamyl acetate and ethyl caproate are the primary aroma compounds responsible for the fruity fragrance characteristic of Ginjo sake. Simultaneous high-level production of both compounds is crucial to achieving a balanced aroma and complex flavor. Isoamyl acetate is predominantly produced by hda1∆/hda1∆ and LEU4(G516S)/LEU4(G516S), while ethyl caproate is produced in high quantities by FAS2(G1250S)/FAS2(G1250S). In this study, to maximize the production of both aroma compounds, genome editing was employed to generate sake yeast strains combining these mutations. After small-scale fermentation tests were conducted to evaluate the production of aroma compounds, we found that the isoamyl acetate-enhancing effect of hda1∆/hda1∆ was almost completely masked by FAS2(G1250S)/FAS2(G1250S). In contrast, the effects of LEU4(G516S)/LEU4(G516S) were not entirely masked by FAS2(G1250S)/FAS2(G1250S), resulting in 2.4- and 5.4-fold greater production of isoamyl acetate and ethyl caproate, respectively. This study highlights the utility of genome editing in the combinatorial breeding of sake yeast.

    DOI： 10.1093/bbb/zbaf029

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  • Identification of novel coenzyme Q10 biosynthetic proteins Coq11 and Coq12 in Schizosaccharomyces pombe Reviewed

    Ikuhisa Nishida, Yuki Ohmori, Ryota Yanai, Shogo Nishihara, Yasuhiro Matsuo, Tomohiro Kaino, Dai Hirata, Makoto Kawamukai

    Journal of Biological Chemistry   299 ( 6 )   104797 - 104797   2023.6

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    Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.jbc.2023.104797

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  • Targeted Mutations Produce Divergent Characteristics in Pedigreed Sake Yeast Strains

    Norapat Klinkaewboonwong, Shinsuke Ohnuki, Tomoya Chadani, Ikuhisa Nishida, Yuto Ushiyama, Saki Tomiyama, Atsuko Isogai, Tetsuya Goshima, Farzan Ghanegolmohammadi, Tomoyuki Nishi, Katsuhiko Kitamoto, Takeshi Akao, Dai Hirata, Yoshikazu Ohya

    Microorganisms   11 ( 5 )   1274 - 1274   2023.5

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    Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

    Modification of the genetic background and, in some cases, the introduction of targeted mutations can play a critical role in producing trait characteristics during the breeding of crops, livestock, and microorganisms. However, the question of how similar trait characteristics emerge when the same target mutation is introduced into different genetic backgrounds is unclear. In a previous study, we performed genome editing of AWA1, CAR1, MDE1, and FAS2 on the standard sake yeast strain Kyokai No. 7 to breed a sake yeast with multiple excellent brewing characteristics. By introducing the same targeted mutations into other pedigreed sake yeast strains, such as Kyokai strains No. 6, No. 9, and No. 10, we were able to create sake yeasts with the same excellent brewing characteristics. However, we found that other components of sake made by the genome-edited yeast strains did not change in the exact same way. For example, amino acid and isobutanol contents differed among the strain backgrounds. We also showed that changes in yeast cell morphology induced by the targeted mutations also differed depending on the strain backgrounds. The number of commonly changed morphological parameters was limited. Thus, divergent characteristics were produced by the targeted mutations in pedigreed sake yeast strains, suggesting a breeding strategy to generate a variety of sake yeasts with excellent brewing characteristics.

    DOI： 10.3390/microorganisms11051274

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  • Genome Editing to Generate Sake Yeast Strains with Eight Mutations That Confer Excellent Brewing Characteristics. International journal

    Tomoya Chadani, Shinsuke Ohnuki, Atsuko Isogai, Tetsuya Goshima, Mao Kashima, Farzan Ghanegolmohammadi, Tomoyuki Nishi, Dai Hirata, Daisuke Watanabe, Katsuhiko Kitamoto, Takeshi Akao, Yoshikazu Ohya

    Cells   10 ( 6 )   2021.5

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    Language：English   Publishing type：Research paper (scientific journal)  

    Sake yeast is mostly diploid, so the introduction of recessive mutations to improve brewing characteristics requires considerable effort. To construct sake yeast with multiple excellent brewing characteristics, we used an evidence-based approach that exploits genome editing technology. Our breeding targeted the AWA1, CAR1, MDE1, and FAS2 genes. We introduced eight mutations into standard sake yeast to construct a non-foam-forming strain that makes sake without producing carcinogens or an unpleasant odor, while producing a sweet ginjo aroma. Small-scale fermentation tests showed that the desired sake could be brewed with our genome-edited strains. The existence of a few unexpected genetic perturbations introduced during breeding proved that genome editing technology is extremely effective for the serial breeding of sake yeast.

    DOI： 10.3390/cells10061299

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  • Effect of koji starter on metabolites in Japanese alcoholic beverage sake made from the sake rice Koshitanrei Reviewed International journal

    Eri Ichikawa, Shougo Hirata, Yuko Hata, Hisashi Yazawa, Hiroyasu Tamura, Mitsuoki Kaneoka, Kazuhiro Iwashita, Dai Hirata

    Bioscience, Biotechnology, and Biochemistry   84 ( 8 )   1714 - 1723   2020.8

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    Language：English   Publishing type：Research paper (scientific journal)  

    In sake brewing, the steamed rice is used in 2 ways, added to sake-mash and making rice-koji. Rice-koji is made from the steamed rice by using koji starter, and its quality is an important determinant of the aroma/taste of sake. The sake rice Koshitanrei (KOS) was developed in Niigata Prefecture by crossing 2 sake rice varieties, Gohyakumangoku and Yamadanishiki. Recently, we reported the characteristic components/metabolites in sake made from KOS by conducting metabolome analysis using UPLC-QTOF-MS. In this study, to investigate the effect of koji starter and sake rice cultivars on the sake metabolites, we performed small-scale sake-making tests using the above 3 rice cultivars and 3 koji starters. Finally, we demonstrated that some of the characteristic components/metabolites of sake from KOS are affected by the koji starter. Thus, in addition to rice cultivar, koji starter plays an important role for establishment/maintenance of the quality of the final product.

    DOI： 10.1080/09168451.2020.1763154

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  • Characteristic analyses of the fermentation and sporulation properties of the traditional sake yeast strain Hiroshima no.6. Reviewed

    R. Yamasaki, T. Goshima, K. Oba, A. Isogai, R. Ohdoi, D. Hirata, T. Akao

    Bioscience, Biotechnology, and Biochemistry   84 ( 4 )   842 - 853   2020.4

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  • Development of sake yeast haploid set with diverse brewing properties using sake yeast strain Hiroshima no. 6 exhibiting sexual reproduction. Reviewed

    R. Yamasaki, T. Goshima, K. Oba, M. Kanai, R. Ohdoi, D. Hirata, T. Akao

    Journal of Bioscience and Bioengineering   129 ( 6 )   706 - 714   2020.2

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  • SKO1 deficiency extends chronological lifespan in Saccharomyces cerevisiae Reviewed

    Masumura, Koji, Matsukami, Sachi, Yonekita, Kumiko, Kanai, Muneyoshi, Kume, Kazunori, Hirata, Dai, Mizunuma, Masaki

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   83 ( 8 )   1473 - 1476   2019.8

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    Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

    Sko1 plays a key role in the control of gene expression by osmotic and oxidative stress in yeast. We demonstrate that the decrease in chronological lifespan (CLS) of hog1 Delta cells was suppressed by SKO1 deletion. sko1 Delta single mutant cells were shown to have a longer CLS, thus implicating Sko1 in the regulation of their CLS.

    DOI： 10.1080/09168451.2019.1571901

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  • Genome editing to generate nonfoam-forming sake yeast strains Reviewed International journal

    S. Ohnuki, M. Kashima, T. Yamada, F. Ghanegolmohammadi, Y. Zhou, T. Goshima, J. Maruyama, K. Kitamoto, D. Hirata, T. Akao, Y. Ohya

    Bioscience, Biotechnology, and Biochemistry   83 ( 8 )   1583 - 1593   2019.8

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    Language：English   Publishing type：Research paper (scientific journal)  

    Mutations frequently occur during breeding of sake yeasts and result in unexpected phenotypes. Here, genome editing tools were applied to develop an ideal nonfoam-forming sake yeast strain, K7GE01, which had homozygous awa1∆/awa1∆ deletion alleles that were responsible for nonfoam formation and few off-target mutations. High-dimensional morphological phenotyping revealed no detectable morphological differences between the genome-edited strain and its parent, while the canonical nonfoam-forming strain, K701, showed obvious morphological changes. Small-scale fermentation tests also showed differences between components of sake produced by K7GE01 and K701. The K7GE01 strain produced sake with significant differences in the concentrations of ethyl acetate, malic acid, lactic acid, and acetic acid, while K701 produced sake with more differences. Our results indicated genuine phenotypes of awa1∆/awa1∆ in sake yeast isolates and showed the usefulness of genome editing tools for sake yeast breeding.

    DOI： 10.1080/09168451.2019.1631146

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  • Analysis of metabolites in Japanese alcoholic beverage sake made from the sake rice Koshitanrei Reviewed International journal

    E. Ichikawa, S. Hirata, Y. Hata, H. Yazawa, H. Tamura, M. Kaneoke, K. Iwashita, D. Hirata

    Bioscience, Biotechnology, and Biochemistry   83 ( 8 )   1570 - 1582   2019.8

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    Language：English   Publishing type：Research paper (scientific journal)  

    In sake brewing, the steamed rice is used in two ways, added to sake-mash (as kake-mai) and making koji. The rice is an important determinant for the quality of sake, as the metabolites in sake affect its taste/aroma. The sake rice Koshitanrei (KOS) was developed in Niigata Prefecture by genetically crossing two sake rice, Gohyakumangoku and Yamadanishiki. However, the metabolites in sake from KOS have not been analyzed. Here, to investigate the characteristic metabolites in sake from KOS, we performed two types of small-scale sake-fermentation tests changing only the rice used for kake-mai or total rice (both kake-mai and koji) by these three rice cultivars and examined the effect of KOS on sake metabolites by the metabolome analysis method using UPLC-QTOF-MS. We identified the peaks/metabolites, whose intensity in sake from KOS was higher/lower than those from the other cultivars. The brewing properties of KOS were partially characterized by this analysis.

    DOI： 10.1080/09168451.2019.1608804

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  • Role of nucleocytoplasmic transport in interphase microtubule organization in fission yeast Reviewed

    Kume, Kazunori, Kaneko, Sayuri, Nishikawa, Kenji, Mizunuma, Masaki, Hirata, Dai

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   503 ( 2 )   1160 - 1167   2018.9

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    Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

    The proper organization of microtubules is essential for many cellular functions. Microtubule organization and reorganization are highly regulated during the cell cycle, but the underlying mechanisms remain elusive. Here we characterized unusual interphase microtubule organization in fission yeast nuclear export mutant crm1-124. The mutant cells have an intranuclear microtubule bundle during interphase that pushes the nuclear envelope to assume a protruding morphology. We showed that the formation of this protruding microtubule bundle requires the nuclear accumulation of two microtubule-associated proteins (MAPs), Alp14/TOG and Mal3/EB1. Interestingly, the forced accumulation of Alp14 in the nucleus of wild type cells is sufficient to form the intranuclear microtubule bundle. Furthermore, the frequency of the intranuclear microtubule formation by Alp14 accumulated in the nucleus is prominently increased by a reduction in the nucleation activity of interphase cytoplasmic microtubules. We propose that properly regulated nucleocytoplasmic transport and maintained activity of cytoplasmic microtubule nucleation during interphase are important for the proper organization of interphase cy

    DOI： 10.1016/j.bbrc.2018.06.135

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  • Evaluation of Palatability of Sake paired with Dishes : A New Endeavor Invited

    中村, 諒, 中野, 久美子, 田村, 博康, 水沼, 正樹, 伏木, 亨, 平田, 大

    日本醸造協会誌 = Journal of the Brewing Society of Japan   113 ( 5 )   282 - 288   2018

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    Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：日本醸造協会  

    type:論文
    「おいしさ」は，「食」に豊かさを付与する楽しみや喜びをともなう感覚的なもの(快感)である。ヒトが感じるおいしさは，複数の因子によって構成され，それらは物性的な要因と非物性的な要因に大別される。前者に関するおいしさの評価法は，味覚の受容体から脳内情報処理に至る経路などの分子基盤も含め，多くの知見が得られ研究が進展している。一方，後者に関するおいしさの評価法はいまだ不明な点が多い。このたび，我々は，チーズにおいて提案された複数の非物性的な要因を統合する総合的なおいしさの評価法を，日本酒のおいしさの評価に適用した。本稿では，料理とともに味わう日本酒のおいしさの評価，その新たな試みについて概略と展望を紹介したい。
    identifier:922470
    identifier:ZZ00020787

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    Other Link： http://id.ndl.go.jp/bib/029066545

  • Systematic analysis of Ca2+ homeostasis in Saccharomyces cerevisiae based on chemical-genetic interaction profiles. Reviewed International journal

    Farzan Ghanegolmohammadi, Mitsunori Yoshida, Shinsuke Ohnuki, Yuko Sukegawa, Hiroki Okada, Keisuke Obara, Akio Kihara, Kuninori Suzuki, Tetsuya Kojima, Nozomu Yachie, Dai Hirata, Yoshikazu Ohya

    Molecular biology of the cell   28 ( 23 )   3415 - 3427   2017.11

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1091/mbc.E17-04-0216

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  • Identification of three signaling molecules required for calcineurin-dependent monopolar growth induced by the DNA replication checkpoint in fission yeast Reviewed

    Kazunori Kume, Tomoyo Hashimoto, Masashi Suzuki, Masaki Mizunuma, Takashi Toda, Dai Hirata

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   491 ( 4 )   883 - 889   2017.9

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.bbrc.2017.07.129

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  • Phenotypic Diagnosis of Lineage and Differentiation During Sake Yeast Breeding. Reviewed International journal

    Shinsuke Ohnuki, Hiroki Okada, Anne Friedrich, Yoichiro Kanno, Tetsuya Goshima, Hirokazu Hasuda, Masaaki Inahashi, Naoto Okazaki, Hiroyasu Tamura, Ryo Nakamura, Dai Hirata, Hisashi Fukuda, Hitoshi Shimoi, Katsuhiko Kitamoto, Daisuke Watanabe, Joseph Schacherer, Takeshi Akao, Yoshikazu Ohya

    G3 (Bethesda, Md.)   7 ( 8 )   2807 - 2820   2017.8

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    Language：English   Publishing type：Research paper (scientific journal)  

    Sake yeast was developed exclusively in Japan. Its diversification during breeding remains largely uncharacterized. To evaluate the breeding processes of the sake lineage, we thoroughly investigated the phenotypes and differentiation of 27 sake yeast strains using high-dimensional, single-cell, morphological phenotyping. Although the genetic diversity of the sake yeast lineage is relatively low, its morphological diversity has expanded substantially compared to that of the Saccharomycescerevisiae species as a whole. Evaluation of the different types of breeding processes showed that the generation of hybrids (crossbreeding) has more profound effects on cell morphology than the isolation of mutants (mutation breeding). Analysis of phenotypic robustness revealed that some sake yeast strains are more morphologically heterogeneous, possibly due to impairment of cellular network hubs. This study provides a new perspective for studying yeast breeding genetics and micro-organism breeding strategies.

    DOI： 10.1534/g3.117.044099

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  • Evaluation of the comprehensive palatability of Japanese sake paired with dishes by multiple regression analysis based on subdomains Reviewed

    Ryo Nakamura, Kumiko Nakano, Hiroyasu Tamura, Masaki Mizunuma, Tohru Fushiki, Dai Hirata

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   81 ( 8 )   1598 - 1606   2017

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1080/09168451.2017.1336924

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  • Stimulating S-adenosyl-L-methionine synthesis extends lifespan via activation of AMPK Reviewed

    Takafumi Ogawa, Ryohei Tsubakiyama, Muneyoshi Kanai, Tetsuya Koyama, Tsutomu Fujii, Haruyuki Iefuji, Tomoyoshi Soga, Kazunori Kume, Tokichi Miyakawa, Dai Hirata, Masaki Mizunuma

    Proc. Natl. Acad. Sci. USA   113 ( 42 )   11913 - 11918   2016.10

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  • Identification of a mutation causing a defective spindle assembly checkpoint in high ethyl caproate-producing sake yeast strain K1801 Reviewed

    Goshima, Tetsuya, Nakamura, Ryo, Kume, Kazunori, Okada, Hiroki, Ichikawa, Eri, Tamura, Hiroyasu, Hasuda, Hirokazu, Inahashi, Masaaki, Okazaki, Naoto, Akao, Takeshi, Shimoi, Hitoshi, Mizunuma, Masaki, Ohya, Yoshikazu, Hirata, Dai

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   80 ( 8 )   1657 - 1662   2016.8

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    Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

    In high-quality sake brewing, the cerulenin-resistant sake yeast K1801 with high ethyl caproate-producing ability has been used widely; however, K1801 has a defective spindle assembly checkpoint (SAC). To identify the mutation causing this defect, we first searched for sake yeasts with a SAC-defect like K1801 and found that K13 had such a defect. Then, we searched for a common SNP in only K1801 and K13 by examining 15 checkpoint-related genes in 23 sake yeasts, and found 1 mutation, R48P of Cdc55, the PP2A regulatory B subunit that is important for the SAC. Furthermore, we confirmed that the Cdc55-R48P mutation was responsible for the SAC-defect in K1801 by molecular genetic analyses. Morphological analysis indicated that this mutation caused a high cell morphological variation. But this mutation did not affect the excellent brewing properties of K1801. Thus, this mutation is a target for breeding of a new risk-free K1801 with normal checkpoint integrity.

    DOI： 10.1080/09168451.2016.1184963

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  • Spatial control of translation repression and polarized growth by conserved NDR kinase Orb6 and RNA-binding protein Sts5 Reviewed

    Nunez, Illyce, Pino, Marbelys Rodriguez, Wiley, David J, Das, Maitreyi, Chen, Chuan, Goshima, Tetsuya, Kume, Kazunori, Hirata, Dai, Toda, Takashi, Verde, Fulvia

    ELIFE   5   2016.7

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    Publishing type：Research paper (scientific journal)   Publisher：ELIFE SCIENCES PUBLICATIONS LTD  

    RNA-binding proteins contribute to the formation of ribonucleoprotein (RNP) granules by phase transition, but regulatory mechanisms are not fully understood. Conserved fission yeast NDR (Nuclear Dbf2-Related) kinase Orb6 governs cell morphogenesis in part by spatially controlling Cdc42 GTPase. Here we describe a novel, independent function for Orb6 kinase in negatively regulating the recruitment of RNA-binding protein Sts5 into RNPs to promote polarized cell growth. We find that Orb6 kinase inhibits Sts5 recruitment into granules, its association with processing (P) bodies, and degradation of Sts5-bound mRNAs by promoting Sts5 interaction with 14-3-3 protein Rad24. Many Sts5-bound mRNAs encode essential factors for polarized cell growth, and Orb6 kinase spatially and temporally controls the extent of Sts5 granule formation. Disruption of this control system affects cell morphology and alters the pattern of polarized cell growth, revealing a role for Orb6 kinase in the spatial control of translational repression that enables normal cell morphogenesis.

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  • Natural thioallyl compounds increase oxidative stress resistance and lifespan in Caenorhabditis elegans by modulating SKN-1/Nrf Reviewed

    Ogawa, Takahiro, Kodera, Yukihiro, Hirata, Dai, Blackwell, T. Keith, Mizunuma, Masaki

    SCIENTIFIC REPORTS   6   2016.2

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    Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

    Identification of biologically active natural compounds that promote health and longevity, and understanding how they act, will provide insights into aging and metabolism, and strategies for developing agents that prevent chronic disease. The garlic-derived thioallyl compounds S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC) have been shown to have multiple biological activities. Here we show that SAC and SAMC increase lifespan and stress resistance in Caenorhabditis elegans and reduce accumulation of reactive oxygen species (ROS). These compounds do not appear to activate DAF-16 (FOXO orthologue) or mimic dietary restriction (DR) effects, but selectively induce SKN-1 (Nrf1/2/3 orthologue) targets involved in oxidative stress defense. Interestingly, their treatments do not facilitate SKN-1 nuclear accumulation, but slightly increased intracellular SKN-1 levels. Our data also indicate that thioallyl structure and the number of sulfur atoms are important for SKN-1 target induction. Our results indicate that SAC and SAMC may serve as potential agents that slow aging.

    DOI： 10.1038/srep21611

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  • A Method for Rapid Identification of the Sake Yeast with High Ethyl Caproate-producing Ability

    Hiroyasu TAMURA, Takashi KURIBAYASHI, Kazunori KUME, Tetsuya GOSHIMA, Ryo NAKAMURA, Ken-ichi WATANABE, Ken AKAO, Hitoshi SHIMOI, Masaki MIZUNUMA, Dai HIRATA

    110 ( 12 )   820 - 826   2015.12

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  • Casein kinase 1 gamma acts as a molecular switch for cell polarization through phosphorylation of the polarity factor Tea1 in fission yeast Reviewed

    Koyano, Takayuki, Barnouin, Karin, Snijders, Ambrosius P, Kume, Kazunori, Hirata, Dai, Toda, Takashi

    GENES TO CELLS   20 ( 12 )   1046 - 1058   2015.12

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    Fission yeast undergoes growth polarity transition from monopolar to bipolar during G2 phase, designated NETO (New End Take Off). It is known that NETO onset involves two prerequisites, the completion of DNA replication and attainment of a certain cell size. However, the molecular mechanism remains unexplored. Here, we show that casein kinase 1 gamma, Cki3 is a critical determinant of NETO onset. Not only did cki3 Delta cells undergo NETO during G1- or S-phase, but they also displayed premature NETO under unperturbed conditions with a smaller cell size, leading to cell integrity defects. Cki3 interacted with the polarity factor Tea1, of which phosphorylation was dependent on Cki3 kinase activity. GFP nanotrap of Tea1 by Cki3 led to Tea1 hyperphosphorylation with monopolar growth, whereas the same entrapment by kinase-dead Cki3 resulted in converse bipolar growth. Intriguingly, the Tea1 interactor Tea4 was dissociated from Tea1 by Cki3 entrapment. Mass spectrometry identified four phosphoserine residues within Tea1 that were hypophosphorylated in cki3 Delta cells. Phosphomimetic Tea1 mutants showed compromised binding to Tea4 and NETO defects, indicating that these serine residues a

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  • Isolation of a spontaneous cerulenin-resistant sake yeast with both high ethyl caproate-producing ability and normal checkpoint integrity Reviewed

    Hiroyasu Tamura, Hiroki Okada, Kazunori Kume, Takayuki Koyano, Tetsuya Goshima, Ryo Nakamura, Takeshi Akao, Hitoshi Shimoi, Masaki Mizunuma, Yoshikazu Ohya, Dai Hirata

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   79 ( 7 )   1191 - 1199   2015.7

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  • Screening for a gene deletion mutant whose temperature sensitivity is suppressed by FK506 in budding yeast and its application for a positive screening for drugs inhibiting calcineurin Reviewed

    Kume, Kazunori, Koyano, Takayuki, Takata, Junpei, Wakabayashi, Ko, Mizunuma, Masaki, Miyakawa, Tokichi, Hirata, Dai

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   79 ( 5 )   790 - 794   2015.5

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    Calcineurin, which is a Ca2+/calmodulin-dependent protein phosphatase, is a key mediator in calcium signaling in diverse biological processes and of clinical importance as the target of the immunosuppressant FK506. To identify a mutant(s) in which calcine

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  • Casein Kinase 1 gamma Ensures Monopolar Growth Polarity under Incomplete DNA Replication Downstream of Cds1 and Calcineurin in Fission Yeast Reviewed

    Koyano, Takayuki, Konishi, Manabu, Martin, Sophie G, Ohya, Yoshikazu, Hirata, Dai, Toda, Takashi, Kume, Kazunori

    MOLECULAR AND CELLULAR BIOLOGY   35 ( 9 )   1533 - 1542   2015.5

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    Cell polarity is essential for various cellular functions during both proliferative and developmental stages, and it displays dynamic alterations in response to intracellular and extracellular cues. However, the molecular mechanisms underlying spatiotemporal control of polarity transition are poorly understood. Here, we show that fission yeast Cki3 (a casein kinase 1 gamma homolog) is a critical regulator to ensure persistent monopolar growth during S phase. Unlike the wild type, cki3 mutant cells undergo bipolar growth when S phase is blocked, a condition known to delay transition from monopolar to bipolar growth (termed NETO [new end takeoff]). Consistent with this role, Cki3 kinase activity is substantially increased, and cells lose their viability in the absence of Cki3 upon an S-phase block. Cki3 acts downstream of the checkpoint kinase Cds1/Chk2 and calcineurin, and the latter physically interacts with Cki3. Autophosphorylation in the C terminus is inhibitory toward Cki3 kinase activity, and calcineurin is responsible for its dephosphorylation. Cki3 localizes to the plasma membrane, and this localization requires the palmitoyltransferase complex Erf2-Erf4. Membrane localizati

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  • The essential function of Rrs1 in ribosome biogenesis is conserved in budding and fission yeasts Reviewed

    Wan, Kun, Kawara, Haruka, Yamamoto, Tomoyuki, Kume, Kazunori, Yabuki, Yukari, Goshima, Tetsuya, Kitamura, Kenji, Ueno, Masaru, Kanai, Muneyoshi, Hirata, Dai, Funato, Kouichi, Mizuta, Keiko

    Yeast   32 ( 9 )   607 - 614   2015

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    The Rrs1 protein plays an essential role in the biogenesis of 60S ribosomal subunits in budding yeast (Saccharomyces cerevisiae). Here, we examined whether the fission yeast (Schizosaccharomyces pombe) homologue of Rrs1 also plays a role in ribosome biogenesis. To this end, we constructed two temperature-sensitive fission yeast strains, rrs1-D14/22G and rrs1-L51P, which had amino acid substitutions corresponding to those of the previously characterized budding yeast rrs1-84 (D22/30G) and rrs1-124 (L61P) strains, respectively. The fission yeast mutants exhibited severe defects in growth and 60S ribosomal subunit biogenesis at high temperatures. In addition, expression of the Rrs1 protein of fission yeast suppressed the growth defects of the budding yeast rrs1 mutants at high temperatures. Yeast two-hybrid analyses revealed that the interactions of Rrs1 with the Rfp2 and Ebp2 proteins were conserved in budding and fission yeasts. These results suggest that the essential function of Rrs1 in ribosome biogenesis may be conserved in budding and fission yeasts. Copyright (c) 2015 John Wiley & Sons, Ltd.

    DOI： 10.1002/yea.3083

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  • Late-maturing cooking rice Sensyuraku has excellent properties, equivalent to sake rice, for high-quality sake brewing Reviewed

    Yoshihiko Anzawa, Kenji Satoh, Yuko Satoh, Satomi Ohno, Tsutomu Watanabe, Kazuaki Katsumata, Kazunori Kume, Ken-ichi Watanabe, Masaki Mizunuma, Dai Hirata

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   78 ( 11 )   1954 - 1962   2014.11

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  • Administered chrysanthemum flower oil attenuates hyperuricemia: mechanism of action as revealed by DNA microarray analysis Reviewed

    Shinichi Honda, Seiji Kawamoto, Hozumi Tanaka, Hideyuki Kishida, Masayasu Kitagawa, Yuji Nakai, Keiko Abe, Dai Hirata

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   78 ( 4 )   655 - 661   2014.4

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  • Polishing Properties of Sake Rice Koshitanrei for High-Quality Sake Brewing Reviewed

    Yoshihiko Anzawa, Yoshihito Nabekura, Kenji Satoh, Yuko Satoh, Satomi Ohno, Tsutomu Watanabe, Mitsuoki Kaneoke, Kazunori Kume, Masaki Mizunuma, Ken-ichi Watanabe, Kazuaki Katsumata, Dai Hirata

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   77 ( 10 )   2160 - 2165   2013.10

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  • Evidence of Antagonistic Regulation of Restart from G(1) Delay in Response to Osmotic Stress by the Hog1 and Whi3 in Budding Yeast Reviewed

    Mizunuma, Masaki, Ogawa, Takafumi, Koyama, Tetsuya, Shitamukai, Atsunori, Tsubakiyama, Ryohei, Komaruyama, Tadamasa, Yamaguchi, Toshinaga, Kume, Kazunori, Hirata, Dai

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   77 ( 10 )   2002 - 2007   2013.10

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    Hog1 of Saccharomyces cerevisiae is activated by hyperosmotic stress, and this leads to cell-cycle delay in G(1), but the mechanism by which cells restart from G(1) delay remains elusive. We found that Whi3, a negative regulator of G(1) cyclin, counteracted Hog1 in the restart from G(1) delay caused by osmotic stress. We have found that phosphorylation of Ser-568 in Whi3 by RAS/cAMP-dependent protein kinase (PKA) plays an inhibitory role in Whi3 function. In this study we found that the phosphomimetic Whi3 S568D mutant, like the Delta whi3 strain, slightly suppressed G(1) delay of Delta hog1 cells under osmotic stress conditions, whereas the non-phosphorylatable S568A mutation of Whi3 caused prolonged G(1) arrest of Delta hog1 cells. These results indicate that Hog1 activity is required for restart from G(1) arrest under osmotic stress conditions, whereas Whi3 acts as a negative regulator for this restart mechanism.

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  • Fission Yeast Leucine-Rich Repeat Protein Lrp1 Is Essential for Cell Morphogenesis as a Component of the Morphogenesis Orb6 Network (MOR) Reviewed

    Kume, Kazunori, Kubota, Shunsuke, Koyano, Takayuki, Kanai, Muneyoshi, Mizunuma, Masaki, Toda, Takashi, Hirata, Dai

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   77 ( 5 )   1086 - 1091   2013.5

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    In eukaryotes, cell morphogenesis is regulated coordinately with the cell cycle. In fission yeast, the morphogenesis network MOR (morphogenesis Orb6 network) consists of 5 conserved proteins, Pmo25, Nak1, Mor2, Orb6, and Mob2, and is essential for cell polarity control and cell separation following cytokinesis. Here we show that the conserved leucine-rich repeat protein Lrp1 is required for cell morphogenesis as a newly recognized component of MOR. Lrp1 has 4 leucine-rich repeats in its N-terminus and is a homolog of the budding yeast Sog2, which is a component of the RAM network (regulation of Ace2 activity and cellular morphogenesis). Lrp1 was essential for both cell growth and cell morphogenesis as were the other MOR components. Lrp1 was localized to the SPBs (spindle pole bodies, the yeast equivalent of the animal centrosome) throughout the cell cycle and to the medial ring during cytokinesis. Lrp1 interacted with Nak1 and was important for Orb6 kinase activity. Thus Lrp1 proved to function upstream of Orb6 in cell morphogenesis.

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  • Ras/cAMP-dependent Protein Kinase (PKA) Regulates Multiple Aspects of Cellular Events by Phosphorylating the Whi3 Cell Cycle Regulator in Budding Yeast Reviewed

    Mizunuma, Masaki, Tsubakiyama, Ryohei, Ogawa, Takafumi, Shitamukai, Atsunori, Kobayashi, Yoshifumi, Inai, Tomomi, Kume, Kazunori, Hirata, Dai

    JOURNAL OF BIOLOGICAL CHEMISTRY   288 ( 15 )   10558 - 10566   2013.4

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    The Start/G(1) phase in the cell cycle is an important period during which cells determine their developmental fate, onset of mitotic progression, or the switch to developmental stages in response to both external and internal signals. In the budding yeast Saccharomyces cerevisiae, Whi3, a negative regulator of the G(1) cyclins, has been identified as a positive regulator of cell size control and is involved in the regulation of Start. However, the regulatory pathway of Whi3 governing the response to multiple signals remains largely unknown. Here, we show that Whi3 is phosphorylated by the Ras/cAMP-dependent protein kinase (PKA) and that phosphorylation of Ser-568 in Whi3 by PKA plays an inhibitory role in Whi3 function. Phosphorylation of Whi3 by PKA led to its decreased interaction with CLN3 G(1) cyclin mRNA and was required for the promotion of G(1)/S progression. Furthermore, we demonstrate that the phosphomimetic S568D mutation of Whi3 prevented the developmental fate switch to sporulation or invasive growth. Thus, PKA modulated the function of Whi3 by phosphorylation, thus implicating PKA-mediated modulation of Whi3 in multiple cellular events.

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  • Isolation of a non-urea-producing sake yeast strain carrying a discriminable molecular marker Reviewed

    Takashi Kuribayashi, Hiroyasu Tamura, Keigo Sato, Yoshihito Nabekura, Toshio Aoki, Yoshihiko Anzawa, Kazuaki Katsumata, Shunji Ohdaira, Susumu Yamashita, Kazunori Kume, Mitsuoki Kaneoke, Ken-Ichi Watanabe, Dai Hirata

    Bioscience, Biotechnology and Biochemistry   77 ( 12 )   2505 - 2509   2013

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  • Analysis of the biological activity of a novel 24-membered macrolide JBIR-19 in Saccharomyces cerevisiae by the morphological imaging program CalMorph Reviewed

    Shinsuke Ohnuki, Tomohide Kobayashi, Hayato Ogawa, Ikuko Kozone, Jun-ya Ueda, Motoki Takagi, Kazuo Shin-ya, Dai Hirata, Satoru Nogami, Yoshikazu Ohya

    FEMS Yeast Research   12 ( 3 )   293 - 304   2012.5

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  • Analysis of free fatty acids in sake by an enzymatic method and its application for estimating ethyl caproate and selecting yeast with high productivity of the ester Reviewed

    Takashi Kuribayashi, Mitsuoki Kaneoke, Dai Hirata, Ken-Ichi Watanabe

    Bioscience, Biotechnology and Biochemistry   76 ( 2 )   391 - 394   2012

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  • Systematic Localization Study on Novel Proteins Encoded by Meiotically Up-Regulated ORFs in Fission Yeast Reviewed

    Chiho Ikebe, Manabu Konishi, Dai Hirata, Takahiro Matsusaka, Takashi Toda

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   75 ( 12 )   2364 - 2370   2011.12

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  • Implication of Ca2+ in the Regulation of Replicative Life Span of Budding Yeast Reviewed

    Ryohei Tsubakiyama, Masaki Mizunuma, Anri Gengyo, Josuke Yamamoto, Kazunori Kume, Tokichi Miyakawa, Dai Hirata

    JOURNAL OF BIOLOGICAL CHEMISTRY   286 ( 33 )   28681 - 28687   2011.8

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  • Sake Lees Fermented with Lactic Acid Bacteria Prevents Allergic Rhinitis-Like Symptoms and IgE-Mediated Basophil Degranulation Reviewed

    Seiji Kawamoto, Mitsuoki Kaneoke, Kayo Ohkouchi, Yuichi Amano, Yuki Takaoka, Kazunori Kume, Tsunehiro Aki, Susumu Yamashita, Ken-ichi Watanabe, Motoni Kadowaki, Dai Hirata, Kazuhisa Ono

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   75 ( 1 )   140 - 144   2011.1

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  • Fission Yeast Germinal Center (GC) Kinase Ppk11 Interacts with Pmo25 and Plays an Auxiliary Role in Concert with the Morphogenesis Orb6 Network (MOR) in Cell Morphogenesis Reviewed

    Goshima, Tetsuya, Kume, Kazunori, Koyano, Takayuki, Ohya, Yoshikazu, Toda, Takashi, Hirata, Dai

    JOURNAL OF BIOLOGICAL CHEMISTRY   285 ( 45 )   35196 - 35205   2010.11

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    How cell morphology and the cell cycle are coordinately regulated is a fundamental subject in cell biology. In fission yeast, 2 germinal center kinases (GCKs), Sid1 and Nak1, play an essential role in septation/cytokinesis and cell separation/cell polarity control, respectively, as components of the septation initiation network (SIN) and the morphogenesis Orb6 network (MOR). Here we show that a third GCK, Ppk11, is also required for efficient cell separation particularly, at a high temperature. Although Ppk11 is not essential for cell division, this kinase plays an auxiliary role in concert with MOR in cell morphogenesis. Ppk11 physically interacts with the MOR component Pmo25 and is localized to the septum, by which Ppk11 is crucial for Pmo25 targeting/accumulation to the septum. The conserved C-terminal WDF motif of Ppk11 is essential for both septum accumulation of Pmo25 and efficient cell separation. In contrast its kinase activity is required only for cell separation. Thus, both interaction of Ppk11 with Pmo25 and Ppk11 kinase activity are critical for efficient cell separation.

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  • The mitosis-to-interphase transition is coordinated by cross talk between the SIN and MOR pathways in Schizosaccharomyces pombe Reviewed

    Ray, Samriddha, Kume, Kazunori, Gupta, Sneha, Ge, Wanzhong, Balasubramanian, Mohan, Hirata, Dai, McCollum, Dannel

    JOURNAL OF CELL BIOLOGY   190 ( 5 )   793 - 805   2010.9

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    The mechanisms that regulate cytoskeletal remodeling during the transition between mitosis and interphase are poorly understood. In fission yeast the MOR pathway promotes actin polarization to cell tips in interphase, whereas the SIN signaling pathway drives actomyosin ring assembly and cytokinesis. We show that the SIN inhibits MOR signaling in mitosis by interfering with Nak1 kinase-mediated activation of the most downstream MOR component, the NDR family kinase Orb6. Inactivation of the MOR may be a key function of the SIN because attenuation of MOR signaling rescued the cytokinetic defects of SIN mutants and allowed weak SIN signaling to trigger ectopic cytokinesis. Furthermore, failure to inhibit the MOR is toxic when the cell division apparatus is compromised. Together, our results reveal a mutually antagonistic relationship between the SIN and MOR pathways, which is important for completion of cytokinesis and coordination of cytoskeletal remodeling at the mitosis-to-interphase transition.

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  • Search for Kinases Related to Transition of Growth Polarity in Fission Yeast Reviewed

    Takayuki Koyano, Kazunori Kume, Manabu Konishi, Takashi Toda, Dai Hirata

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   74 ( 5 )   1129 - 1133   2010.5

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  • Identification of Tup1 and Cyc8 mutations defective in the responses to osmotic stiress Reviewed

    Kobayashi, Yoshifumi, Inai, Tomomi, Mizunuma, Masaki, Okada, Ichitaro, Shitamukai, Atsunori, Hirata, Dai, Miyakawa, Tokichi

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   368 ( 1 )   50 - 55   2008.3

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    In the yeast Saccharomyces cerevisiae, Tup1, in association with Cyc8 (Ssn6), functions as a general transcriptional corepressor. This repression is mediated by recruitment of the Tup1-Cyc8 complex to target promoters through sequence-specific DNA-binding proteins such as Sko1, which mediates the HOG pathway-dependent regulation. We identified tup1 and cyc8 mutant alleles as the suppressor of osmo-sensitivity of the hog1 Delta strain. In these mutants, although the expression of the genes under the control of DNA-binding proteins other than Sko1 was apparently normal, the Sko1-regulated genes GRE2 and AHP1 were derepressed under non-stress conditions, suggesting that the Tup1 and Cyc8 mutant proteins were specifically defective in the repression of the Sko1-dependent genes. Chromatin immunoprecipitation analyses of the GRE2 promoter in the mutants demonstrated that the Sko1-Tup1-Cyc8 complex was localized to the promoter, together with Gcn5/SAGA, suggesting that the erroneous recruitment of SAGA to the promoter led to the derepression. (C) 2008 Elsevier Inc. All rights reserved.

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  • Diversity of Ca2+-induced morphology revealed by morphological phenotyping of Ca2+-sensitive mutants of Saccharomyces cerevisiae Reviewed

    Shinsuke Ohnuki, Satoru Nogami, Hanako Kanai, Dai Hirata, Yoichiro Nakatani, Shinichi Morishita, Yoshikazu Ohya

    EUKARYOTIC CELL   6 ( 5 )   817 - 830   2007.5

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  • A method for Pmo25-associated kinase assay in fission yeast: The activity is dependent on two GC kinases Nak1 and Sid1 Reviewed

    Kume, Kazunori, Goshima, Tetsuya, Miyahara, Kohji, Toda, Takashi, Hirata, Dai

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   71 ( 2 )   615 - 617   2007.2

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    In fission yeast, the conserved proteins, MO25/ Pmo25, GC kinase/Nak1, Furry/Mor2, NDR kinase/ Orb6, and Mob2, constitute the morphogenesis Orb6 network (MOR). Previously we showed that Pmo25 functions as an upstream component of MOR and that it plays a connecting role between the septation initiation network (SIN) and MOR. Here we establish a Pmo25-associated kinase assay and show that the activity is dependent on Nak1/MOR and Sid1/SIN.

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  • Involvement of calcineurin-dependent degradation of Yap1p in Ca2+-induced G(2) cell-cycle regulation in Saccharomyces cerevisiae Reviewed

    Yokoyama, H, Mizunuma, M, Okamoto, M, Yamamoto, J, Hirata, D, Miyakawa, T

    EMBO REPORTS   7 ( 5 )   519 - 524   2006.5

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    The Ca2+-activated pathways in Saccharomyces cerevisiae induce a delay in the onset of mitosis through the activation of Swe1p, a negative regulatory kinase that inhibits the Cdc28p/Clb complex. We isolated the YAP1 gene as a multicopy suppressor of calcium sensitivity owing to the loss of ZDS1, a negative regulator of SWE1 and CLN2 gene expression. YAP1 deletion on a zds1 Delta background exacerbated the Ca2+-related phenotype. Yap1p was degraded in a calcineurin-dependent manner when cells were exposed to calcium. In yap1 Delta cells, the expression level of the RPN4 gene encoding a transcription factor for the subunits of the ubiquitin-proteasome system was diminished. The deletion of YAP1 gene or RPN4 gene led to the accumulation of Swe1p and Cln2p. Yap1p was a substrate of calcineurin in vivo and in vitro. The calcineurin-mediated Yap1p degradation seems to be a long adaptive response that assures a G(2) delay in response to a stress that causes the activation of the calcium signalling pathways.

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  • The V260I mutation in fission yeast alpha-tubulin Atb2 affects microtubule dynamics and EB1-Mal3 localization and activates the Bub1 branch of the spindle checkpoint. Reviewed

    Asakawa K, Kume K, Kanai M, Goshima T, Miyahara K, Dhut S, Tee WW, Hirata D, Toda T

    Molecular biology of the cell   17 ( 3 )   1421 - 1435   2006.3

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  • Evaluation of image processing programs for accurate measurement of budding and fission yeast morphology Reviewed

    Suzuki Genjiro, Sawai Hiroshi, Ohtani Miwaka, Nogami Satoru, Sano-Kumagai Fumi, Saka Ayaka, Yukawa Masashi, Saito Taro L, Sese Jun, Hirata Dai, o

    Current genetics   49 ( 4 )   237 - 247   2006

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  • Mal3, the fission yeast EB1 homologue, cooperates with Bub1 spindle checkpoint to prevent monopolar attachment. Reviewed

    Asakawa K, Toya M, Sato M, Kanai M, Kume K, Goshima T, Garcia MA, Hirata D, Toda T

    EMBO reports   6   1194 - 1200   2005.12

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  • Implication of Pkc1p protein kinase C in sustaining Cln2p level and polarized bud growth in response to calcium signaling in Saccharomyces cerevisiae Reviewed

    M Mizunuma, D Hirata, T Miyakawa

    JOURNAL OF CELL SCIENCE   118 ( 18 )   4219 - 4229   2005.9

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  • Mutational analysis of the yeast multidrug resistance ABC transporter Pdr5p with altered drug specificity Reviewed

    AC Tutulan-Cunita, M Mikoshi, M Mizunuma, D Hirata, T Miyakawa

    GENES TO CELLS   10 ( 5 )   409 - 420   2005.5

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  • Involvement of Saccharomyces cerevisiae Pdr5p ATP-binding cassette transporter in calcium homeostasis Reviewed

    AC Tutulan-Cunita, T Ohnishi, M Mizunuma, D Hirata, T Miyakawa

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   69 ( 4 )   857 - 860   2005.4

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  • 酵母の特殊な変異形質を利用するCa^<2+>シグナル伝達に作用する薬剤のポジティブスクリーニング

    下向 敦範, 水沼 正樹, 平田 大, 高橋 英俊, 宮川 都吉

    日本農芸化学会誌   76 ( 8 )   734 - 735   2002.8

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  • 酵母の特殊な変異形質を利用するCa2+シグナル伝達に作用する薬剤のポジティブスクリーニング Invited

    下向 敦範, 水沼 正樹, 平田 大, 高橋 英俊, 宮川 都吉

    化学と生物(日本農芸化学会誌)   76   38 - 39   2002

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  • Regulation of Wee1 kinase in response to protein synthesis inhibition Reviewed

    M Suda, S Yamada, T Toda, T Miyakawa, D Hirata

    FEBS LETTERS   486 ( 3 )   305 - 309   2000.12

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  • Yeast Crv4/Ttp1, a predicted type II membrane protein, is involved in an event important for growth, functionally overlapping with the event regulated by calcineurin- and Mpk1-mediated pathways Reviewed

    T. Nakamura, T. Ohmoto, D. Hirata, E. Tsuchiya, T. Miyakawa

    Molecular Genetics and Genomics   256 ( 5 )   481 - 487   1997.11

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Books

  • 清酒酵母の研究 90年代の研究

    大嶋泰治, 大隅良典, 平田 大（ Role： Joint author）

    財団法人日本醸造協会  2003.2 

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    Total pages：202   Responsible for pages：39-46   Language：Japanese Book type：Scholarly book

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  • バイオテクノロジー講義

    宮川都吉, 平田 大（ Role： Joint author）

    朝倉書店  1999.2 

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    Total pages：156   Responsible for pages：59-64   Language：Japanese Book type：Textbook, survey, introduction

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  • 酵母とバイオ 酵母研究の新潮流

    大隅良典, 松本邦弘, 田中一馬, 宮川都吉, 中村太郎, 平田 大（ Role： Joint author）

    医学出版センター  1994.1 

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    Total pages：305   Responsible for pages：28-42   Language：Japanese Book type：Scholarly book

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MISC

  • Involvement of S-adenosylmethionine in G(1) cell-cycle regulation in Saccharomyces cerevisiae

    M Mizunuma, K Miyamura, D Hirata, H Yokoyama, T Miyakawa

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   101 ( 16 )   6086 - 6091   2004.4

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  • Fission yeast Mor2/Cps12, a protein similar to Drosophila Furry, is essential for cell morphogenesis and its mutation induces Wee1-dependent G(2) delay

    D Hirata, N Kishimoto, M Suda, Y Sogabe, S Nakagawa, Y Yoshida, K Sakai, M Mizunuma, T Miyakawa, J Ishiguro, T Toda

    EMBO JOURNAL   21 ( 18 )   4863 - 4874   2002.9

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  • Role of calcineurin and Mpk1 in regulating the onset of mitosis in budding yeast

    M Mizunuma, D Hirata, K Miyahara, E Tsuchiya, T Miyakawa

    NATURE   392 ( 6673 )   303 - 306   1998.3

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  • Essential role of tubulin-folding cofactor D in microtubule assembly and its association with microtubules in fission yeast

    D Hirata, H Masuda, M Eddison, T Toda

    EMBO JOURNAL   17 ( 3 )   658 - 666   1998.2

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  • Polishing/Brewing Properties of Sake Rice Koshitanrei for High-Quality Sake Brewing Invited

    110 ( 3 )   120 - 125   2015.3

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

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    Other Link： http://agriknowledge.affrc.go.jp/RN/2010891549

  • 1P-151 Isolation of a spontaneous cerulenin-resistant sake yeast with high ethyl caproate-producing ability

    Tamura Hiroyasu, Kuribayashi Takashi, Kume Kazunori, Goshima Tetsuya, Nakamura Ryo, Ichikawa Eri, Watanabe Ken-ichi, Akao Takeshi, Shimoi Hitoshi, Mizunuma Masaki, Hirata Dai

    67   126 - 126   2015

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  • 出芽酵母の寿命研究の現状と展望 Invited

    水沼正樹, 平田 大

    日本醸造協会誌   106 ( 12 )   794 - 800   2011.12

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  • DNA複製と細胞極性をつなぐ経路：癌細胞の異常な形を理解するヒント！ Invited

    久米一規, 平田 大

    細胞工学   30 ( 8 )   854 - 855   2011.8

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  • 分裂酵母の２つのHippo関連経路のクロストーク Invited

    久米一規, 五島徹也, 平田 大

    実験医学   29 ( 3 )   445 - 448   2011.3

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  • 分裂酵母の細胞形態形成 Invited

    久米一規, 平田 大, 登田 隆

    酵母のすべて   243 - 248   2007.9

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  • ストレス応答性MAPキナーゼ経路とCa2+シグナル伝達 Invited

    宮川都吉, 平田 大, 水沼正樹

    酵母のすべて   293 - 299   2007.9

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  • Effect of ethanol on cell growth of budding yeast: Genes that are important for cell growth in the presence of ethanol

    S Kubota, Takeo, I, K Kume, M Kanai, A Shitamukai, M Mizunuma, T Miyakawa, H Shimoi, H Iefuji, D Hirata

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   68 ( 4 )   968 - 972   2004.4

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    Language：English   Publisher：TAYLOR & FRANCIS LTD  

    The budding yeast Saccharomyces cerevisiae has been used in the fermentation of various kinds of alcoholic beverages. But the effect of ethanol on the cell growth of this yeast is poorly understood. This study shows that the addition of ethanol causes a cell-cycle delay associated with a transient dispersion of F-actin cytoskeleton, resulting in an increase in cell size. We found that the tyrosine kinase Swe1, the negative regulator of Cdc28-Clb kinase, is related to the regulation of cell growth in the presence of ethanol. Indeed, the increase in cell size due to ethanol was partially abolished in the SWE1-deleted cells, and the amount of Swe1 protein increased transiently in the presence of ethanol. These results indicated that Swe1 is involved in cell size control in the presence of ethanol, and that a signal produced by ethanol causes a transient up-regulation of Swe1. Further we investigated comprehensively the ethanol-sensitive strains in the complete set of 4847 non-essential gene deletions and identified at least 256 genes that are important for cell growth in the presence of ethanol.

    DOI： 10.1271/bbb.68.968

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  • Effect of ethanol on cell growth of budding yeast: Genes that are important for cell growth in the presence of ethanol

    S Kubota, Takeo, I, K Kume, M Kanai, A Shitamukai, M Mizunuma, T Miyakawa, H Shimoi, H Iefuji, D Hirata

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   68 ( 4 )   968 - 972   2004.4

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  • Evidence for antagonistic regulation of cell growth by the calcineurin and high osmolarity glycerol pathways in Saccharomyces cerevisiae

    A Shitamukai, D Hirata, S Sonobe, T Miyakawa

    JOURNAL OF BIOLOGICAL CHEMISTRY   279 ( 5 )   3651 - 3661   2004.1

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  • Coordinated Regulation of Cell Morphogenesis and Cell Cycle

    KANAI Muneyoshi, HIRATA Dai

    化学と生物   41 ( 10 )   651 - 656   2003.10

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    DOI： 10.1271/kagakutoseibutsu1962.41.651

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  • A novel function of Saccharomyces cerevisiae PKC1 in the regulation of polarized bud growth.

    M Mizunuma, D Hirata, T Miyakawa

    YEAST   20   S262 - S262   2003.7

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  • Mechanism of antagonistic growth regulation by the high-osmolarity glycerol pathway and Ca2+-signaling pathways in budding yeast.

    A Shitamukai, T Yamaguchi, D Hirata, T Miyakawa

    YEAST   20   S260 - S260   2003.7

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  • 細胞のサイズを決める分子機構 Invited

    須田雅子, 平田 大

    バイオサイエンスとインダストリー   61 ( 3 )   181 - 184   2003.3

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  • Identification of Saccharomyces cerevisiae isoleucyl-tRNA synthetase as a target of the G(1)-specific inhibitor reveromycin A

    Y Miyamoto, K Machida, M Mizunuma, Y Emoto, N Sato, K Miyahara, D Hirata, T Usui, H Takahashi, H Osada, T Miyakawa

    JOURNAL OF BIOLOGICAL CHEMISTRY   277 ( 32 )   28810 - 28814   2002.8

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  • 2001年ノーベル医学生理学賞 細胞分裂制御の謎を解く-３人の細胞周期研究者 Invited

    平田 大

    化学   57 ( 1 )   36 - 39   2002.1

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  • 進化する酵母 -Fission Yeast Invited

    平田 大, 桐沢和恒, 須田雅子

    細胞工学   21 ( 1 )   25 - 30   2002.1

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  • The role of Pdr5 ABC transporter in regulating cellular calcium.

    AC Cunita, T Ohnishi, M Mizunuma, D Hirata, T Miyakawa

    YEAST   18   S269 - S269   2001.8

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  • A positive screening for the drugs that suppresses Ca2+ signaling in yeast.

    N Sato, A Shitamukai, E Aihara, M Mizunuma, D Hirata, T Miyakawa

    YEAST   18   S298 - S298   2001.8

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  • A novel function of Saccharomyces cerevisiae PKC1 in the regulation of G(2)/M transition.

    M Mizunuma, D Hirata, T Miyakawa

    YEAST   18   S155 - S155   2001.8

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  • Antagonistic growth regulation by Hog1 and Ca2+ signaling pathway in budding yeast.

    A Shitamukai, D Hirata, SY Sonobe, T Miyakawa

    YEAST   18   S145 - S145   2001.8

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  • Conserved Wat1/Pop3 WD-repeat protein of fission yeast secures genome stability through microtubule integrity and may be involved in mRNA maturation

    IL Ochotorena, D Hirata, K Kominami, J Potashkin, F Sahin, K Wentz-Hunter, KL Gould, K Sato, Y Yoshida, L Vardy, T Toda

    JOURNAL OF CELL SCIENCE   114 ( 16 )   2911 - 2920   2001.8

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  • Fission yeast homologues of the B ' subunit of protein phosphatase 2A: multiple roles in mitotic cell division and functional interaction with calcineurin

    O Tanabe, D Hirata, H Usui, Y Nishito, T Miyakawa, K Igarashi, M Takeda

    GENES TO CELLS   6 ( 5 )   455 - 473   2001.5

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  • 酵母を使った生理活性物質の新規スクリーニング法 Invited

    平田 大, 下向敦範, 水沼正樹, 宮川都吉

    生物工学会誌   79 ( 3 )   79 - 79   2001.3

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  • GSK-3 kinase Mck1 and calcineurin coordinately mediate Hsl1 down-regulation by Ca2+ in budding yeast

    M Mizunuma, D Hirata, R Miyaoka, T Miyakawa

    EMBO JOURNAL   20 ( 5 )   1074 - 1085   2001.3

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  • Fission yeast homologues of the Bﾕ subunit of protein phosphatase 2A: multiple roles in mitotic cell division and functional interaction with calcineurin.

    Genes Cells   6 ( 5 )   455 - 473   2001

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  • Regulation of Wee1 kinase in response to protein synthesis inhibition

    Masako Suda, Shinya Yamada, Takashi Toda, Tokichi Miyakawa, Dai Hirata

    FEBS Letters   486 ( 3 )   305 - 309   2000.12

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  • A positive screening for drugs that specifically inhibit the Ca2+-signaling activity on the basis of the growth promoting effect on a yeast mutant with a peculiar phenotype. International journal

    A Shitamukai, M Mizunuma, D Hirata, H Takahashi, T Miyakawa

    Bioscience, biotechnology, and biochemistry   64 ( 9 )   1942 - 6   2000.9

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    An inappropriate activation of a signaling pathway in yeast often has a deleterious physiological effect and causes various defects, including growth defects. In a certain genetic background (deltazds1) of Saccharomyces cerevisiae, the cell-cycle progression in G2 is specifically blocked in the medium with CaCl2 by the hyperactivation of the Ca2+-signaling pathways. Here, we developed a novel drug screening procedure designed to detect the active compounds that specifically attenuate the Ca2+-signaling activity on the basis of the ability to abrogate the growth defect of the cells suffering from the hyperactivated Ca2+ signal. Using known calcineurin inhibitors as model compounds, we have established the screening conditions for the drugs that suppress the Ca2+-induced growth inhibition. An indicator strain with an increased drug sensitivity was constructed with a syr1/erg3 null mutation.

    DOI： 10.1271/bbb.64.1942

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  • Ca2+シグナルによる細胞周期制御機構 Invited

    水沼正樹, 平田 大, 宮川都吉

    実験医学   18 ( 7 )   10 - 15   2000.7

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  • Regulation of Weel kinase in response to protein synthesis inhibition

    SUDA M.

    FEBS Lett.   486 ( 3 )   305 - 309   2000

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  • Involvement of thioredoxin peroxidase type II (Ahp1p) of Saccharomyces cerevisiae in Mn2+ homeostasis

    IC Farcasanu, D Hirata, E Tsuchiya, K Mizuta, T Miyakawa

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   63 ( 11 )   1871 - 1881   1999.11

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  • Functional dissection and hierarchy of tubulin-folding cofactor homologues in fission yeast

    PA Radcliffe, D Hirata, L Vardy, T Toda

    MOLECULAR BIOLOGY OF THE CELL   10 ( 9 )   2987 - 3001   1999.9

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  • 酵母遺伝子破壊形質を利用する生理活性物質のポジチブスクリーニング Invited

    宮川都吉, 下向敦範, 平田 大, 高橋英俊

    生物工学会誌   77 ( 9 )   406 - 408   1999.9

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  • Functional dissection and hierarchy of tubulin-folding cofactor homologues in fission yeast

    PA Radcliffe, D Hirata, L Vardy, T Toda

    MOLECULAR BIOLOGY OF THE CELL   10 ( 9 )   2987 - 3001   1999.9

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    Language：English   Publisher：AMER SOC CELL BIOLOGY  

    We describe the isolation of fission yeast homologues of tubulin-folding cofactors B (Alp11) and E (Alp21), which are essential for cell viability and the maintenance of microtubules. Alp11B contains the glycine-rich motif (the CLIP-170 domain) involved in microtubular functions, whereas, unlike mammalian cofactor E, Alp21(E) does not. both mammalian and yeast cofactor E, however, do contain leucine-rich repeats. Immunoprecipitation analysis shows that Alp11(B) interacts with both a-tubulin and Alp21(E), but not with the cofactor D homologue Alp1, whereas Alp21(E) also interacts with Alpl(D). The cellular amount of a-tubulin is decreased in both alp1 and alp(11) mutants. Overproduction of Alp11(B) results in cell lethality and the disappearance of microtubules, which is rescued by co-overproduction of alpha-tubulin. Both hull-length Alp11(B) and the C-terminal third containing the CLIP-170 domain localize in the cytoplasm, and this domain is required for efficient binding to alpha-tubulin. Deletion of alp11 is suppressed by multicopy plasmids containing either alp21(+) or alp(1+), whereas alp(21) deletion is rescued by overexpression of either alp11(+) or alp21(+). The alp1(+) but not alp11(+). Finally, the alp1 mutant is not complemented by either alp11(+) or alp21(+). The results suggest that cofactors operate in a linear pathway (Alp11(B)-Alp21(E)-Alp(D)), each with distinct roles.

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  • Overproduction of elongation factor 1 alpha, an essential translational component, causes aberrant cell morphology by affecting the control of growth polarity in fission yeast

    M Suda, M Fukui, Y Sogabe, K Sato, A Morimatsu, R Arai, F Motegi, T Miyakawa, Mabuchi, I, D Hirata

    GENES TO CELLS   4 ( 9 )   517 - 527   1999.9

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  • Ca^<2+>シグナルによる出芽酵母細胞周期G_2制御および制御ネットワーク

    宮川 都吉, 水沼 正樹, 宮岡 理恵, 園部 晋也, 平田 大

    日本農芸化学会誌   73   462 - 462   1999.3

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  • Fission yeast alpha-glucan synthase Mok1 requires the actin cytoskeleton to localize the sites of growth and plays an essential role in cell morphogenesis downstream of protein kinase C function

    S Katayama, D Hirata, M Arellano, P Perez, T Toda

    JOURNAL OF CELL BIOLOGY   144 ( 6 )   1173 - 1186   1999.3

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  • Fission yeast alpha-glucan synthase Mok1 requires the actin cytoskeleton to localize the sites of growth and plays an essential role in cell morphogenesis downstream of protein kinase C function

    S Katayama, D Hirata, M Arellano, P Perez, T Toda

    JOURNAL OF CELL BIOLOGY   144 ( 6 )   1173 - 1186   1999.3

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    Language：English   Publisher：ROCKEFELLER UNIV PRESS  

    In fission yeast protein kinase C homologues (Pck1 and Pck2) are essential for cell morphogenesis. We have isolated mok1(+) in a genetic screen to identify downstream effecters for Pck1/2. mok1(+) is essential for viability and encodes a protein that has several membrane-spanning domains and regions homologous to glucan metabolic enzymes. mok1 mutant shows abnormal cell shape, randomization of F-actin and weak cell wall. Biochemical analysis shows that Mok1 appears to have a-glucan synthase activity. Mok1 localization undergoes dramatic alteration during the cell cycle. It localizes to the growing tips in interphase, the medial ring upon mitosis, a double ring before and dense dot during cytokinesis. Double immunofluorescence staining shows that Mok1 exists in close proximity to actin. The subcellular localization of Mok1 is dependent upon the integrity of the F-actin cytoskeleton. Conversely, overexpression of mok1(+) blocks the translocation of cortical actin from one end of the cell to the other. pck2 mutant is synthetically lethal with mok1 mutant, delocalizes Mok1 and shows a lower level of alpha-glucan. These results indicate that Mok1 plays a crucial role in cell morphogenesis interdependently of the actin cytoskeleton and works as one of downstream effecters for Pck1/2.

    DOI： 10.1083/jcb.144.6.1173

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  • 新規の細胞周期チェックポイント制御とMAPキナーゼ Invited

    平田 大, 水沼正樹, 宮川都吉

    実験医学   17 ( 2 )   124 - 129   1999.2

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  • Functional analysis of the promoter of the yeast SNQ2 gene encoding a multidrug resistance transporter that confers the resistance to 4-nitroquinoline N-oxide

    ZF Cui, D Hirata, T Miyakawa

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   63 ( 1 )   162 - 167   1999.1

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  • Essential molecules for cell growth in yeast: Control of cell proliferation by calcium-signaling pathway

    Dai Hirata

    Nippon Nogeikagaku Kaishi   73 ( 9 )   887 - 892   1999

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    Language：Japanese   Publisher：Japan Society for Bioscience Biotechnology and Agrochemistry  

    DOI： 10.1271/nogeikagaku1924.73.887

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  • Control of cell cycle progression by calcium-slgnaling pathways in budding yeast :

    HIRATA Dai, MIZUNUMA Masaki, MIYAKAWA Tokichi

    Journal of radiation research   40 ( 4 )   356 - 356   1999

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    Other Link： https://projects.repo.nii.ac.jp/?action=repository_uri&item_id=235685

  • Isolation and characterization of DSL genes that suppress the synthetic lethality of Δcnb1Δmpk1 disruptant

    OKAMOTO Michiyo, HIRATA Dai, SONOBE Shinya, MIYAKAWA Tokichi

    21   552 - 552   1998.12

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  • Regulation of cell-cycle progression by Ca^<2+>-signalling pathways in budding yeast

    HIRATA Dai, MIZUNUMA Masaki, MIYAKAWA Tokichi

    21   181 - 181   1998.12

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  • Isolation and characterization of suppressor mutants of zds1 mutation which exhibits Ca^<2+>-induced abnormal cell morphology in Saccharomyces cerevisiae

    MIZUNUMA Masaki, HIRATA Dai, MIYAOKA Rie, OHNISHI Tomoko, MIYAKAWA Tokichi

    21   502 - 502   1998.12

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  • Identification of EF1αas a gene whose overexpression disturbs the establishment and the maintenance of growth polarity in fission yeast

    SUDA Masako, FUKUI Mikiko, SATO Kazuhito, SOGABE Yuki, MIYAKAWA Tokichi, HIRATA Dai

    21   502 - 502   1998.12

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  • Implication of Hog1MAPK in the cell-cycle control mediated by calcineurin and Mpk1MAPK

    SONOBE Shinya, HIRATA Dai, OKAMOTO Michiyo, MIYAKAWA Tokichi

    21   552 - 552   1998.12

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  • アクチン、チューブリンと細胞周期チェックポイント Invited

    平田 大, 登田 隆

    細胞工学   17 ( 12 )   1897 - 1905   1998.12

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  • Involvement of histidine permease (Hip1p) in manganese transport in Saccharomyces cerevisiae

    IC Farcasanu, M Mizunuma, D Hirata, T Miyakawa

    MOLECULAR AND GENERAL GENETICS   259 ( 5 )   541 - 548   1998.9

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  • Yeast gene YRR1, which is required for resistance to 4-nitroquinoline N-oxide, mediates transcriptional activation of the multidrug resistance transporter gene SNQ2

    Z Cui, T Shiraki, D Hirata, T Miyakawa

    MOLECULAR MICROBIOLOGY   29 ( 5 )   1307 - 1315   1998.9

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  • Identification of novel temperature-sensitive lethal alleles in essential beta-tubulin and nonessential alpha 2-tubulin genes as fission yeast polarity mutants

    P Radcliffe, D Hirata, D Childs, L Vardy, T Toda

    MOLECULAR BIOLOGY OF THE CELL   9 ( 7 )   1757 - 1771   1998.7

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  • Functional interaction of Isr1, a predicted protein kinase, with the Pkc1 pathway in Saccharomyces cerevisiae

    K Miyahara, D Hirata, T Miyakawa

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   62 ( 7 )   1376 - 1380   1998.7

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  • 酵母における細胞形態形成機構の分子生物学的解析 Invited

    平田 大

    日本農芸化学会誌   72 ( 6 )   772 - 773   1998.6

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    DOI： 10.1271/nogeikagaku1924.72.772

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  • Genes that cause aberrant cell morphology by overexpression in fission yeast: a role of a small GTP-binding protein Rho2 in cell morphogenesis

    D Hirata, K Nakano, M Fukui, H Takenaka, T Miyakawa, Mabuchi, I

    JOURNAL OF CELL SCIENCE   111   149 - 159   1998.1

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  • Genes that cause aberrant cell morphology by overexpression in fission yeast: A role of a small GTP-binding protein Rho2 in cell morphogenesis

    Dai Hirata, Kentaro Nakano, Mikiko Fukui, Hiroshi Takenaka, Tokichi Miyakawa, Issei Mabuchi

    Journal of Cell Science   111 ( 2 )   149 - 159   1998

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  • Yeast gene YRR1, which is required for resistance to 4-nitroquinoline N-oxide, mediates transcriptional activation of the multidrug resistance transporter gene SNQ2.

    Mol. Microbiol.   29 ( 5 )   1307 - 1315   1998

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  • Functional interaction of isr1, a predicted protein kinase, with the pkc1 pathway in saccharomyces cerevisiae

    Kohji Miyahara, Dai Hirata, Tokichi Miyakawa

    Bioscience, Biotechnology and Biochemistry   62 ( 7 )   1376 - 1380   1998

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  • Yeast Crv4/Ttp1, a predicted type II membrane protein, is involved in an event important for growth, functionally overlapping with the event regulated by calcineurin- and Mpk1-mediated pathways

    T Nakamura, T Ohmoto, D Hirata, E Tsuchiya, T Miyakawa

    MOLECULAR & GENERAL GENETICS   256 ( 5 )   481 - 487   1997.11

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  • Mutational analysis of Yap1 protein, an AP-1-like transcriptional activator of Saccharomyces cerevisiae

    T Takeuchi, K Miyahara, D Hirata, T Miyakawa

    FEBS LETTERS   416 ( 3 )   339 - 343   1997.10

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    To define the essential amino acid residues of Yap1 in stress response, we generated yap1 mutations by in vitro mutagenesis, which cause defects in mediating resistance to the stress of H2O2, hut not of CdCl2. Sequence analysis of the mutant yap1 genes revealed three point mutations and two truncation mutations near the carboxy-terminus. The truncation mutations resulted in hyperresistance to cadmium, Northern blot analysis of stress-induced levels of TRX2 and GSH1 mRNAs indicated that the ability of the mutant Yap1 protein to induce transcriptional activation of target genes correlates well with its ability to confer stress resistance, The carboxy-terminal domain of Yap1 appears to act negatively in cadmium resistance. (C) 1997 Federation of European Biochemical Societies.

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  • Mutational analysis of Yap1 protein, an AP-1-like transcriptional activator of Saccharomyces cerevisiae

    T Takeuchi, K Miyahara, D Hirata, T Miyakawa

    FEBS LETTERS   416 ( 3 )   339 - 343   1997.10

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  • Multidrug resistance ABC transporter of yeast

    T Miyakawa, D Hirata, K Miyahara

    NIPPON NOGEIKAGAKU KAISHI-JOURNAL OF THE JAPAN SOCIETY FOR BIOSCIENCE BIOTECHNOLOGY AND AGROCHEMISTRY   71 ( 8 )   808 - 811   1997.8

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  • 出芽酵母の多剤耐性ABCトランスポーター Invited

    宮川都吉, 平田 大, 宮原浩二

    日本農芸化学会誌   71 ( 8 )   808 - 811   1997.8

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    DOI： 10.1271/nogeikagaku1924.71.808

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  • Yeast Crv4/Ttp1, a predicted type II membrane protein, is involved in an event important for growth, functionally overlapping with the event regulated by calcineurin- and Mpk1- mediated pathways.

    Mol. Gen. Genet.   256 ( 5 )   481 - 487   1997

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  • 細胞形態形成 Invited

    平田 大, 登田 隆

    蛋白質核酸酵素   41 ( 12 )   1927 - 1935   1996.12

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  • The involvement of the Saccharomyces cerevisiae multidrug resistance transporters Pdr5p and Snq2p in cation resistance

    K Miyahara, M Mizunuma, D Hirata, E Tsuchiya, T Miyakawa

    FEBS LETTERS   399 ( 3 )   317 - 320   1996.12

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    平田 大, 登田 隆

    細胞工学   15 ( 12 )   1698 - 1704   1996.12

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  • 酵母のカルシニューリン情報伝達 Invited

    平田 大, 中村太郎, 宮川都吉

    蛋白質核酸酵素   41 ( 12 )   1695 - 1703   1996.12

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  • Microtubules mediate mitochondrial distribution in fission yeast

    MP Yaffe, D Harata, F Verde, M Eddison, T Toda, P Nurse

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   93 ( 21 )   11664 - 11668   1996.10

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  • The fission yeast sts5(+) gene is required for maintenance of growth polarity and functionally interacts with protein kinase C and an osmosensing MAP-kinase pathway

    T Toda, H Niwa, T Nemoto, S Dhut, M Eddison, T Matsusaka, M Yanagida, D Hirata

    JOURNAL OF CELL SCIENCE   109   2331 - 2342   1996.9

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  • 出芽酵母の転写活性化因子yAP-1を介する情報伝達系の解析

    竹内 倫徳, 宮原 浩二, 平田 大, 宮川 都吉

    日本分子生物学会年会プログラム・講演要旨集   19   450 - 450   1996.8

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  • 酵母における必須元素マンガンのホメオスタシス制御機構

    水沼 正樹, FARCASANU Ileana c., 平田 大, 土屋 英子, 宮川 都吉

    日本分子生物学会年会プログラム・講演要旨集   19   275 - 275   1996.8

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  • 広範な有機アニオンの耐性に関与する出芽酵母のMRP様ABCトランスポーターYrs1とその転写制御因子Yrr1

    崔 志峰, 江本 勇治, 平田 大, 土屋 英子, 高橋 英俊, 長田 裕之, 宮川 都吉

    日本分子生物学会年会プログラム・講演要旨集   19   275 - 275   1996.8

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  • 出芽酵母のG2期調節遺伝子NPS1の構造と機能

    細谷 智規, 平田 大, 土屋 英子, 宮川 都吉

    日本分子生物学会年会プログラム・講演要旨集   19   805 - 805   1996.8

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  • 出芽酵母のG2期調節遺伝子NPS1の減数分裂における発現とその調節

    湯川 格史, 平田 大, 土屋 英子, 宮川 都吉

    日本分子生物学会年会プログラム・講演要旨集   19   647 - 647   1996.8

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  • The multidrug resistance-associated protein (MRP) subfamily (Yrs1/Yor1) of Saccharomyces cerevisiae is important for the tolerance to a broad range of organic anions

    ZF Cui, D Hirata, E Tsuchiya, H Osada, T Miyakawa

    JOURNAL OF BIOLOGICAL CHEMISTRY   271 ( 25 )   14712 - 14716   1996.6

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  • Genetic evidence for the functional redundancy of the calcineurin and Mpk1-mediated pathways in the regulation of cellular events important for growth in Saccharomyces cerevisiae

    T Nakamura, T Ohmoto, D Hirata, E Tsuchiya, T Miyakawa

    MOLECULAR & GENERAL GENETICS   251 ( 2 )   211 - 219   1996.5

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  • 酵母の多剤耐性遺伝子のYDRIの薬剤特異性に関する変異の解析 : 微生物

    見越 淳, 宮原 浩二, 平田 大, 宮川 都吉

    日本農藝化學會誌   70   111 - 111   1996.3

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  • Calcineurin-mediated signalling important for adaptation to stress conditions in Saccharomyces cerevisiae : Signal transduction and cell cycle : (S-9)

    Miyakawa Tokichi, Hirata Dai, Nakamura Taro, Farcasanu Ileana

    Journal of the Agricultural Chemical Society of Japan   70   383 - 383   1996.3

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  • リベロマイシン耐性に関与する転写因子をコードする酵母遺伝子YRR1 : 微生物

    江本 勇治, 白木 利幸, 平田 大, 土屋 英子, 高橋 英俊, 長田 裕之, 宮川 都吉

    日本農藝化學會誌   70   270 - 270   1996.3

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  • 酵母Saccharomyces cerevisiaeのカルシニユーリンを介する情報伝達系の解析 : 細胞内Na^+濃度制御系を中心として : 微生物

    中村 太郎, 山口 裕司, 平田 大, 土屋 英子, 宮川 都吉

    日本農藝化學會誌   70   269 - 269   1996.3

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  • NPS1pと酵母の新しい多機能蛋白NPS2pの相互作用の解析 : 微生物

    湯川 格史, 平田 大, 土屋 英子, 宮川 都吉

    日本農藝化學會誌   70   269 - 269   1996.3

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  • 多様な有機アニオンの毒性緩和に必要な酵母のABCトランスポーターYrs1 : 微生物

    崔 志峰, 平田 大, 土屋 英子, 高橋 英俊, 長田 裕之, 宮川 都吉

    日本農藝化學會誌   70   270 - 270   1996.3

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  • 酵母における必須微量重金属マンガンの細胞内ホメオスタシス維持機構の解析 : 微生物

    水沼 正樹, Farasanu Ileana C., 中村 太郎, 平田 大, 土屋 英子, 宮川 都吉

    日本農藝化學會誌   70   270 - 270   1996.3

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  • AP-1ホモログyAP1, yAP2の関与するYDRI転写誘導機構の解析 : 微生物

    宮原 浩二, 平田 大, 宮川 都吉

    日本農藝化學會誌   70   112 - 112   1996.3

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  • 出芽酵母AP-1様転写因子YAP1, YAP2が関与する情報伝達系 : 微生物

    竹内 倫徳, 平田 大, 宮川 都吉

    日本農藝化學會誌   70   105 - 105   1996.3

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  • 酵母のG2期調節遺伝子NPS1の減数分裂における機能の解析 : 微生物

    加藤 聰子, 細谷 智規, 土屋 英子, 平田 大, 宮川 都吉

    日本農藝化學會誌   70   132 - 132   1996.3

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  • 酵母の多機能な核蛋白をコードするNPS2は胞子形成に必須な遺伝子である : 微生物

    土屋 英子, 平田 大, 宮川 都吉

    日本農藝化學會誌   70   132 - 132   1996.3

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  • yAP-1- and yAP-2-mediated, heat shock-induced transcriptional activation of the multidrug resistance ABC transporter genes in Saccharomyces cerevisiae

    K Miyahara, D Hirata, T Miyakawa

    CURRENT GENETICS   29 ( 2 )   103 - 105   1996.1

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  • The multidrug resistance-associated protein (MRP) subfamily of ATP-binding superfamily transporter (Yrs1/Yor1) is important for the tolerance of yeast to a broad range of organic anions.

    J. Biol. Chem.   271   14712 - 14716   1996

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  • Genetic evidence for the functional redundancy of the calcineurin- and Mpk1-mediated pathways in the regulation of cellular events important for growth in Sccharomyces cerevisiae.

    Mol. Gen. Genet.   251 ( 2 )   211 - 219   1996

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  • Calcineurin-mediated signalling important for growth regulation in yeast

    D. Hirata, T. Nakamura, T. Miyakawa

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme   41 ( 12 )   1695 - 1703   1996

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  • ADAPTATION TO HIGH-SALT STRESS IN SACCHAROMYCES-CEREVISIAE IS REGULATED BY CA2+/CALMODULIN-DEPENDENT PHOSPHOPROTEIN PHOSPHATASE (CALCINEURIN) AND CAMP-DEPENDENT PROTEIN-KINASE

    D HIRATA, S HARADA, H NAMBA, T MIYAKAWA

    MOLECULAR & GENERAL GENETICS   249 ( 3 )   257 - 264   1995.11

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  • CLONING AND CHARACTERIZATION OF THE SACCHAROMYCES-CEREVISIAE SVS1 GENE WHICH ENCODES A SERINE-RICH AND THREONINE-RICH PROTEIN REQUIRED FOR VANADATE RESISTANCE

    T NAKAMURA, H NAMBA, T OHMOTO, YS LIU, D HIRATA, T MIYAKAWA

    GENE   165 ( 1 )   25 - 29   1995.11

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  • PROTEIN PHOSPHATASE 2B OF SACCHAROMYCES-CEREVISIAE IS REQUIRED FOR TOLERANCE TO MANGANESE, IN BLOCKING THE ENTRY OF IONS INTO THE CELLS

    IC FARCASANU, D HIRATA, E TSUCHIYA, F NISHIYAMA, T MIYAKAWA

    EUROPEAN JOURNAL OF BIOCHEMISTRY   232 ( 3 )   712 - 717   1995.9

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  • 酵母の多剤耐性トランスポーターによるイオン輸送 : 微生物

    宮原 浩二, 平田 大, 宮川 都吉

    日本農藝化學會誌   69   226 - 226   1995.7

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  • 細胞増殖制御物質リベロマイシン耐性変異遺伝子の解析 : 微生物

    白木 利幸, 崔 志峰, 平田 大, 土屋 英子, 高橋 英俊, 長田 裕之, 宮川 都吉

    日本農藝化學會誌   69   40 - 40   1995.7

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  • 細胞増殖制御物質リベロマイシン感受性変異を相補する酵母Saccharomyces cerevisiaeの遺伝子YRS1の解析 : 微生物

    崔 志峰, 平田 大, 土屋 英子, 高橋 英俊, 長田 裕之, 宮川 都吉

    日本農藝化學會誌   69   40 - 40   1995.7

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  • 酵母のG2期調節遺伝子NPS1の産物は新規なMAR結合蛋白である : 微生物

    岡田 智行, 土屋 英子, 平田 大, 宮川 都吉

    日本農藝化學會誌   69   39 - 39   1995.7

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  • Ca^<2+>シグナルとcAMPシグナルのクロストークにより制御される酵母PMR2遺伝子(Na^+排出ポンプ)の転写誘導 : 微生物

    平田 大, 原田 伸一, 難波 宏光, 宮川 都吉

    日本農藝化學會誌   69   110 - 110   1995.7

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  • 酵母のAP-1ホモログYAP1を介する情報伝達系の解明 : 微生物

    竹内 倫徳, 平田 大, 宮川 都吉

    日本農藝化學會誌   69   225 - 225   1995.7

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  • 酵母のカルシニューリンとMAPキナーゼカスケードの遺伝学的関係 : 微生物

    中村 太郎, 大本 朋良, 平田 大, 土屋 英子, 宮川 都吉

    日本農藝化學會誌   69   225 - 225   1995.7

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  • 酵母におけるMn^<2+>取り込みのカルシニューリンによる制御 : 微生物

    Farcasanu Ileana, 平田 大, 土屋 英子, 宮川 都吉

    日本農藝化學會誌   69   226 - 226   1995.7

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  • カチオンホメオスタシスに関与する酵母遺伝子の解析 : 微生物

    原田 伸一, 荻野 剛, 平田 大, 土屋 英子, 宮川 都吉

    日本農藝化學會誌   69   225 - 225   1995.7

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  • A NOVEL PROTEIN-KINASE GENE SSP1(+) IS REQUIRED FOR ALTERATION OF GROWTH POLARITY AND ACTIN LOCALIZATION IN FISSION YEAST

    T MATSUSAKA, D HIRATA, M YANAGIDA, T TODA

    EMBO JOURNAL   14 ( 14 )   3325 - 3338   1995.7

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  • THE PHYSIOLOGICAL ROLES OF MEMBRANE ERGOSTEROL AS REVEALED BY THE PHENOTYPES OF SYR1/ERG3 NULL MUTANT OF SACCHAROMYCES-CEREVISIAE

    K HEMMI, C JULMANOP, D HIRATA, E TSUCHIYA, JY TAKEMOTO, T MIYAKAWA

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   59 ( 3 )   482 - 486   1995.3

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  • FUNCTIONAL-ANALYSIS OF THE PROMOTER OF THE SACCHAROMYCES-CEREVISIAE MULTIDRUG-RESISTANCE GENE YDR1, WHICH ENCODES A MEMBER OF THE ATP BINDING CASSETTE (ABC) SUPERFAMILY

    K MIYAHARA, D HIRATA, T MIYAKAWA

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   59 ( 1 )   147 - 149   1995.1

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    DOI： 10.1271/bbb.59.147

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  • The Physiological Roles of Membrane Ergosterol as Revealed by the Phenotypes of syr1/erg3 Null Mutant of Saccharomyces cerevisiae

    Kenji Hemmi, Charnchai Julmanop, Dai Hirata, Eiko Tsuchiya, Jon Y. Takemoto, Tokichi Miyakawa

    Bioscience, Biotechnology and Biochemistry   59 ( 3 )   482 - 486   1995

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  • Saccharomyces cerevisiae YDR1, which encodes a member of the ATP-binding cassette (ABC) superfamily, is required for multidrug resistance

    Dai Hirata, Kiichiro Yano, Kohji Miyahara, Tokichi Miyakawa

    Current Genetics   26 ( 4 )   285 - 294   1994.10

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    DOI： 10.1007/BF00310491

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  • 酵母のストレス応答とカルシニューリン Invited

    宮川都吉, 中村太郎, 平田 大

    蛋白質核酸酵素   39 ( 4 )   420 - 428   1994.4

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  • 酵母のストレス応答とカルシニュ-リン--細胞内イオン濃度の調節による高NaClへの適応 (酵母に見る最新の真核生物像--酵母実験系への誘い) -- (信号伝達)

    宮川 都吉, 中村 太郎, 平田 大

    蛋白質核酸酵素   39 ( 4 )   p420 - 428   1994.3

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  • Stress-induced transcriptional activation mediated by YAP1 and YAP2 genes that encode the Jun family of transcriptional activators in Saccharomyces cerevisiae

    Dai Hirata, Kiichiro Yano, Tokichi Miyakawa

    MGG Molecular &amp; General Genetics   242 ( 3 )   250 - 256   1994.2

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    DOI： 10.1007/BF00280413

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  • OVEREXPRESSION AND SECRETION OF CELLULOLYTIC ENZYMES BY DELTA-SEQUENCE-MEDIATED MULTICOPY INTEGRATION OF HETEROLOGOUS DNA-SEQUENCES INTO THE CHROMOSOMES OF SACCHAROMYCES-CEREVISIAE

    D MOCHIZUKI, K MIYAHARA, D HIRATA, H MATSUZAKI, T HATANO, S FUKUI, T MIYAKAWA

    JOURNAL OF FERMENTATION AND BIOENGINEERING   77 ( 5 )   468 - 473   1994

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  • Calcineurin-mediated adaptation to salt stress in yeast

    T. Miyakawa, T. Nakamura, D. Hirata

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme   39 ( 4 )   420 - 428   1994

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  • PROTEIN PHOSPHATASE TYPE-2B (CALCINEURIN)-MEDIATED, FK506-SENSITIVE REGULATION OF INTRACELLULAR IONS IN YEAST IS AN IMPORTANT DETERMINANT FOR ADAPTATION TO HIGH-SALT STRESS CONDITIONS

    T NAKAMURA, YS LIU, D HIRATA, H NAMBA, S HARADA, T HIROKAWA, T MIYAKAWA

    EMBO JOURNAL   12 ( 11 )   4063 - 4071   1993.11

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  • ISOLATION AND CHARACTERIZATION OF SSE1 AND SSE2, NEW MEMBERS OF THE YEAST HSP70 MULTIGENE FAMILY

    H MUKAI, T KUNO, H TANAKA, D HIRATA, T MIYAKAWA, C TANAKA

    GENE   132 ( 1 )   57 - 66   1993.9

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    Two new members of the Saccharomyces cerevisiae heat-shock protein 70 multigene (HSP70) family were isolated from a yeast expression library using antisera made against a yeast calmodulin-binding fraction. They are designated as SSE1 and, SSE2, because their predicted amino acid (aa) sequences are highly homologous to each other (76% identical), and share homology with known members of the yeast HSP70 multigene family, but their homologies (13 to 28% identity) are not high enough to place them in known subfamilies. SSE1 and SSE2 are thought to encode polypeptides of 693 aa with calculated M(r)'s of 77408 and 77619, respectively. The SSE1 mRNAs were moderately abundant during steady-state growth at 23-degrees-C, and increased a few-fold upon upshift to 37-degrees-C. SSE2 mRNAs were present at low level during steady-state growth at 23-degrees-C, and greatly increased upon upshift to 37-degrees-C. Disruption of SSE1 results in slow-growing cells at any temperature. No phenotypic effects of the mutation in SSE2 were detected, and the growth property of the sse1sse2 double mutant was the same as that of the sse1 single mutant.

    DOI： 10.1016/0378-1119(93)90514-4

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  • ISOLATION AND CHARACTERIZATION OF SSE1 AND SSE2, NEW MEMBERS OF THE YEAST HSP70 MULTIGENE FAMILY

    H MUKAI, T KUNO, H TANAKA, D HIRATA, T MIYAKAWA, C TANAKA

    GENE   132 ( 1 )   57 - 66   1993.9

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  • Protein phosphatase 2B (calcineurin)-mediated, FK506-sensitive regulation of intracellular ions in yeast is an important determinant for adaptation to high salt stress conditions.

    EMBO J.   12   4063 - 4071   1993

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  • STABLE OVERPRODUCTION OF ISOAMYL ALCOHOL BY SACCHAROMYCES-CEREVISIAE WITH CHROMOSOME-INTEGRATED MULTICOPY LEU4 GENES

    D HIRATA, S AOKI, K WATANABE, M TSUKIOKA, T SUZUKI

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   56 ( 10 )   1682 - 1683   1992.10

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    Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    DOI： 10.1271/bbb.56.1682

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  • BREEDING OF A USEFUL STRAIN OF SAKE YEAST FOR GINJO-SAKE BREWING

    D HIRATA, S AOKI, K WATANABE, M TSUKIOKA, T SUZUKI

    JOURNAL OF FERMENTATION AND BIOENGINEERING   73 ( 6 )   497 - 499   1992

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    Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：SOC FERMENTATION BIOENGINEERING, JAPAN  

    A useful sake-fermenting yeast for brewing ginjo-sake was bred by protoplast fusion. First, 61 native strains were isolated from ginjo-sake mash. From these isolates, two strains, YNS50 and YNS59, were selected. These two strains possessed many of the characteristics required for ginjo-sake brewing in a complementary manner. Strain YNS50 produced high amounts of the flavor components isoamyl acetate and ethyl caproate and low amounts of acids. Strain YNS59, on the other hand, exhibited good growth and fermentation at low temperatures (approximately 10-degrees-C) and had high resistance to ethyl alcohol. Next, a lysine auxotrophic mutant (YDH17) of YNS50 and rho-mutant (YDH8) of YNS59 with a marker useful for the selection of the fusants were constructed. Finally, prototrophs arising from the complementation of each marker by protoplast fusion were obtained. A strain (strain YNF74) that stably maintained all of the useful characteristics derived from each wild type strain was screened from 120 fusants. In a sub-industrial scale sake brewing test, we demonstrated that strain YNF74 exhibited its superior characteristics in brewing ginjo-sake. The sake produced by strain YNF74 achieved high evaluation in a tasting test.

    DOI： 10.1016/0922-338X(92)90145-K

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  • SECRETION OF THE GLUCOAMYLASE-BETA-LACTAMASE CHIMERA PROTEIN BY SACCHAROMYCES-CEREVISIAE

    D HIRATA, T MIYAKAWA, YAMASHITA, I

    JOURNAL OF FERMENTATION AND BIOENGINEERING   74 ( 4 )   251 - 253   1992

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    Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    DOI： 10.1016/0922-338X(92)90122-B

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  • BREEDING OF A USEFUL STRAIN OF SAKE YEAST FOR GINJO-SAKE BREWING

    D HIRATA, S AOKI, K WATANABE, M TSUKIOKA, T SUZUKI

    JOURNAL OF FERMENTATION AND BIOENGINEERING   73 ( 6 )   497 - 499   1992

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    DOI： 10.1016/0922-338X(92)90145-K

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  • Secretion of the glucoamylase-β-lactamase chimera protein by Saccharomyces cerevisiae

    Dai Hirata, Tokichi Miyakawa, Ichiro Yamashita

    Journal of Fermentation and Bioengineering   74 ( 4 )   251 - 253   1992

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  • GENES THAT CAUSE OVERPRODUCTION OF ISOAMYL ALCOHOL BY INCREASED GENE-DOSAGE EFFECT IN SACCHAROMYCES-CEREVISIAE

    D HIRATA, T HIROI

    AGRICULTURAL AND BIOLOGICAL CHEMISTRY   55 ( 4 )   919 - 924   1991.4

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    Language：English   Publisher：JAPAN SOC BIOSCI BIOTECHN AGROCHEM  

    Isoamyl acetate, one of the major components of flavor in a Japanese brewing product, sake, contributes to the fruity flavor of sake. We cloned Saccharomyces cerevisiae genes that cause overproduction of isoamyl alcohol, the precursor of isoamyl acetate, by increased gene-dosage effect. Three plasmids, pScFlr1, pScFlr2, and pScFlr3, were obtained by selection from the yeast genomic DNA which, on a multicopy plasmid, confer a phenotype resistant to 5,5,5-trifluoro-DL-leucine, an analogue of leucine. The cloned DNA fragments in the three plasmids had different restriction maps. Transformed cells with each of the plasmids produced large amounts of both isoamyl alcohol and isoamyl acetate. The gene cloned in the plasmid pScFlr1 was identified as the LEU4 gene encoding alpha-isopropylmalate synthase.

    DOI： 10.1271/bbb1961.55.919

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  • GENES THAT CAUSE OVERPRODUCTION OF ISOAMYL ALCOHOL BY INCREASED GENE-DOSAGE EFFECT IN SACCHAROMYCES-CEREVISIAE

    D HIRATA, T HIROI

    AGRICULTURAL AND BIOLOGICAL CHEMISTRY   55 ( 4 )   919 - 924   1991.4

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  • NUCLEOTIDE-SEQUENCE OF THE SECRETABLE ACID PROTEASE GENE PEP1 IN THE YEAST SACCHAROMYCOPSIS-FIBULIGERA

    D HIRATA, S FUKUI, YAMASHITA, I

    AGRICULTURAL AND BIOLOGICAL CHEMISTRY   52 ( 10 )   2647 - 2649   1988.10

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    Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：JAPAN SOC BIOSCI BIOTECHN AGROCHEM  

    DOI： 10.1271/bbb1961.52.2647

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  • NUCLEOTIDE-SEQUENCE OF THE SECRETABLE ACID PROTEASE GENE PEP1 IN THE YEAST SACCHAROMYCOPSIS-FIBULIGERA

    D HIRATA, S FUKUI, YAMASHITA, I

    AGRICULTURAL AND BIOLOGICAL CHEMISTRY   52 ( 10 )   2647 - 2649   1988.10

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    DOI： 10.1271/bbb1961.52.2647

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  • CLONING AND EXPRESSION IN SACCHAROMYCES-CEREVISIAE OF THE SECRETABLE ACID PROTEASE GENE FROM SACCHAROMYCOPSIS-FIBULIGERA

    YAMASHITA, I, D HIRATA, M MACHIDA, S FUKUI

    AGRICULTURAL AND BIOLOGICAL CHEMISTRY   50 ( 1 )   109 - 113   1986.1

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    Language：English   Publisher：JAPAN SOC BIOSCI BIOTECHN AGROCHEM  

    DOI： 10.1271/bbb1961.50.109

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  • CLONING AND EXPRESSION IN SACCHAROMYCES-CEREVISIAE OF THE SECRETABLE ACID PROTEASE GENE FROM SACCHAROMYCOPSIS-FIBULIGERA

    YAMASHITA, I, D HIRATA, M MACHIDA, S FUKUI

    AGRICULTURAL AND BIOLOGICAL CHEMISTRY   50 ( 1 )   109 - 113   1986.1

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Awards

  • Biosci.Biotechnol.Biochem.論文賞(2017)

    2018.3   日本農芸化学会  

    平田 大 他

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    Award type：Honored in official journal of a scientific society, scientific journal  Country：Japan

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  • Biosci.Biotechnol.Biochem.論文賞(2000)

    2001.3   日本農芸化学会  

    平田 大 他

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    Award type：Honored in official journal of a scientific society, scientific journal  Country：Japan

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  • 日本農芸化学会奨励賞(1999年度)

    1999.3   日本農芸化学会  

    平田 大

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    Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

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Research Projects

  • 寿命制御における細胞極性制御経路の役割

    Grant number：21K05377

    2021.4 - 2024.3

    System name：科学研究費助成事業

    Research category：基盤研究(C)

    Awarding organization：日本学術振興会

    平田 大

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    Grant amount：\4030000 （ Direct Cost: \3100000 、 Indirect Cost：\930000 ）

    （１）背景（意義・重要性）：細胞極性制御やチェックポイント機構は、細胞の正常な機能発現や遺伝情報の完全性の維持に必須で、その破綻は細胞癌化・老化の一要因である。一方、寿命制御機構の解明は、健康寿命の延伸のみならず老化に伴う癌や生活習慣病の発症機構の解明・予防にとって極めて重要である。
    （２）目的：本研究では申請者がモデル細胞・酵母において発見した細胞極性制御経路について、寿命制御機構との関連性について解析する。具体的には、酵母の細胞極性制御経路（関連分子を含む）について、環境変化に適応する寿命制御機構との関連性を調査し、健康長寿延伸のための基盤研究を展開する。
    （３）実施状況：昨年度は研究実施計画に基づき以下の２つの研究テーマについて研究を展開した。テーマ１ ）環境変化に応答する細胞挙動の解析：一定の環境条件において、環境変化に応答する酵母細胞の生存率を解析した。テーマ２ ）環境適応寿命における細胞極性制御経路の重要性の調査：情報伝達関連分子（細胞極性制御経路関連分子を含む）について、機能欠損変異体を用いて、テーマ１ の環境条件での細胞挙動を調べ、当該分子の寿命制御との関連性を調査した。

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  • 細胞極性を制御するチェックポイント経路に関する基礎および応用研究

    Grant number：24380057

    2012.4 - 2015.3

    System name：科学研究費助成事業

    Research category：基盤研究(B)

    Awarding organization：日本学術振興会

    平田 大

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    Grant amount：\13520000 （ Direct Cost: \10400000 、 Indirect Cost：\3120000 ）

    細胞極性は、増殖や分化と連動し適切に制御され、細胞の機能発現に必須である。一方、チェックポイント機構は、遺伝情報の完全性の維持に必須で、その破綻は、細胞癌化の一要因である。本研究代表者は、これまで、細胞の癌化機構の解明を最終目的として、ヒトのモデル細胞である酵母（分裂、出芽の両酵母）を使って、細胞極性と細胞周期との連携制御機構を解析し、その中で、最近、DNA複製チェックポイント経路（Cds1 kinase）がカルシニューリン（CN:Ca2+/calmodulin-dependent protein phosphatase）を介し、細胞極性を制御する、CCT経路（Cds1-CN-TIPs）を発見した。そこで、本研究では、細胞極性を制御する本チェックポイント経路の解明と普遍性の検証（基礎研究）、本経路を標的とする医薬探索系の開発（応用研究）をめざし、健康長寿に貢献する酵母研究を展開する。各テーマの本年の研究実績を以下に期す。１）細胞極性を制御するチェックポイント経路の解明（基礎研究）：前年度までに同定した、CCT経路の上流および下流で機能する分子について、論文投稿の準備を開始した。２）細胞極性制御分子を標的とする医薬探索系の開発（応用研究）：前年度までに選択したCCT経路の活性を検出可能な変異体を用いた新規医薬探索系について、論文投稿の準備を開始した。

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  • Basic and applied research on cell polarity control yeast

    Grant number：20380063

    2008 - 2011

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    HIRATA Dai, MIZUNUMA Masaki, KUME Kazunori

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    Grant amount：\19240000 （ Direct Cost: \14800000 、 Indirect Cost：\4440000 ）

    In this study, we analyzed the coordinated regulation between cell polarity and the cellcycle in yeast. We have identified a novel molecule in the MOR(Morphogenesis Orb6 Network) pathway that is important for establishment/ maintenance of cell polarity in fission yeast, and showed that the mitosis-to-interphase transition is coordinated by crosstalk between the SIN(Septation Initiation Network) and MOR pathways. Further, we found a new CCT(Cds1-Calcineurin-TIPs) pathway, in which calcineurin ensures a link between the DNA replication checkpoint and microtubule-dependent polarized growth in fission yeast. As all the molecules in the CCT pathway are conserved ubiquitously, it is hoped that the similar mechanism is operational in human beings and new cancer therapeutics would be developed based upon this finding.

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  • Cell cycle regulation of cell morphology and cell size

    Grant number：19057002

    2007 - 2012

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research on Priority Areas

    Awarding organization：Japan Society for the Promotion of Science

    OHYA Yoshikazu, HIRATA Dai

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    Grant amount：\79000000 （ Direct Cost: \79000000 ）

    Cell wall integrity checkpoint is one of the cell cycle checkpoints in Saccharomyces cerevisiae. When the cell wall synthesis is perturbed, cell cycle progression stopped before nuclear division. We identified 18 genes involved in the cell wall integrity checkpoint. We showed that the checkpoint required the kinase signaling pathway that transduced signal from the cell wall to the nucleus. We also showed that phosphorylation of the transcription factor is also important for regulation of G2/M cyclin, a key regulatory factor of the checkpoint.

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  • 神経高次機能における細胞極性ネットワークの役割

    Grant number：17657064

    2005 - 2007

    System name：科学研究費助成事業

    Research category：萌芽研究

    Awarding organization：日本学術振興会

    平田 大

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    Grant amount：\3400000 （ Direct Cost: \3400000 ）

    本研究では、嗅覚順応行動における、進化上保存された細胞極性ネットワークの重要性を実証するため、2つのモデル生物(酵母と線虫)を使って研究している。本年度は以下の知見を得た。
    1.酵母の細胞極性ネットワークの解析:これまでに、分裂酵母の細胞極性ネットワークMOR (Morphogenesis Orb6 network)を同定し、MORが細胞質分裂の開始を制御するSIN (Septation Initiation Network)の制御下にあること(M. Kanai, et. al., EMBO J. 2005)、MORの最上流分子Pmo25に結合するkinase活性が、Nak1/MORとSid1/SINの二つのGC kinaseに依存することを見出している(K. Kume, et. al., Biosci. Biotech. Biochem 2007)。本年度は、新たなMOR構成分子として新規GC kinase Ppk11を同定し、その機能を解析した(投稿中)。
    2.線虫の嗅覚順応変異体の解析:これまでに、GTP結合タンパク質の情報伝達経路の制御分子が、嗅覚順応行動に重要であること、最下流で機能する神経伝達物質の放出を制御する分子を同定している。本年度は、神経伝達物質を特定した(投稿中)。
    3.線虫の嗅覚順応行動におけるSAX2の役割:これまでに、線虫のSAX2が、AWC感覚神経が関与する嗅覚順応行動に特異的に重要であること、SAX2と上記のGTP結合タンパク質の情報伝達経路が機能的に関連することを見出した。本年度は、その詳細についてさらに解析を進めた(投稿準備中)。

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  • A novel checkpoint monitoring growth polarity

    Grant number：16370087

    2004 - 2006

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    HIRATA Dai

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    Grant amount：\15500000 （ Direct Cost: \15500000 ）

    Cell polarity is coordinately regulated during cell cycle and is important for cellular function of individual cells. In this research, we studied a novel checkpoint monitoring growth polarity in yeast. Our findings are as follows.
    1) Activation of cell morphogenesis checkpoint by ethanol: We have analyzed the effect of ethanol on cell morphology of yeast and found that ethanol disrupts actin-cytoskeleton transiently and induces the delay in G2. This result indicated that ethanol activates cell morphogenesis checkpoint in yeast.
    2) Morphogenesis network from SPB: In fission yeast, the conserved proteins, MO25-like Pmo25, GC kinase Nak1, Mor2, and Orb6, constitute a morphogenesis Orb6 network (MOR) for polarity control and cell separation. Pmo25 was localized at the mitotic spindle pole bodies (SPBs) and then underwent translocation to the dividing medial region upon cytokinesis. Pmo25 formed a complex with Nakl and was required for Nakl-Orb6 kinase activity. Further, the Pmo25 localization at the SPBs and the Nakl-Orb6 kinase activities during interphase were under the control of the Cdc7 and Sidl kinases in the septation initiation network (SIN), suggesting a functional linkage between SIN and MOR for cell morphogenesis/separation following cytokinesis.
    3) Activation of the Bubl-dependent checkpoint by а-tubulin mutation: We have identified a novel temperature-sensitive mutant of fission yeast a-tubulin Atb2 (atb2-983) that contains a single amino acid substitution (V260I). Atb2-983 is incorporated into the microtubules, and their overall structures are not altered noticeably, but microtubule dynamics is compromised during interphase. The results indicate that the V260I mutation affects microtubule dynamics and EB1-Mal3 localization and activates the Bubl branch of the spindle checkpoint.
    4) Image processing programs for accurate measurement of yeast morphology: To describe yeast morphology objectively, we have developed image processing programs for budding and fission yeast. Using this program, we can easily and quickly obtain various quantitative data reproducibly.

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  • Cell cycle regulation by Ca2+ and its physiological role in yeast

    Grant number：14206012

    2002 - 2004

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (A)

    Awarding organization：Japan Society for the Promotion of Science

    MIYAKAWA Tokichi, HIRATA Dai, MIZUNUMA Masaki

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    Grant amount：\51220000 （ Direct Cost: \39400000 、 Indirect Cost：\11820000 ）

    To investigate cell cycle regulation by Ca2+ signaling in the yeast Saccharomyces cerevisiae, we isolated many mutants defective in this process and molecular genetic analysis of each mutant was performed. Major outcome are as follows.
    (1)The isolation of the mutants and their genetic characterization.
    In addition to the previously characterized 15 complementation groups we further identified 7 new complementation groups to have 22 groups in total.
    (2)Molecular genetic characterization of scz13 mutant :
    scz13 mutation was identified as an allele of SAH1 gene that encodes S-adenosylhomocystein (AdoHcy) hydrolase. We have demonstrated that the cellular levels of AdoHcy and its precursor S-adenosylmethionine were highly elevated and cell growth of this mutant was arrested in G1 phase. Due to the elevation of cellular levels of AdoHcy and AdoMet, the expression levels of CLN2 and SWE1 were strongly suppressed. The results indicated the involvement of AdoHcy and AdoMet in cell cycle regulation.
    (3)Molecular genetic characterization of scz13 mutant :
    scz6 mutation was identified as an allele of a unique PKC1 gene that encodes protein kinase C in yeast. Pkc1 of yeast is known to be involved in the regulation of Mpk1 MAP kinase cascade, which regulates the synthesis of cell wall. We have shown that the defect of scz6 mutant was in the function different from the previously known Pkc1 function. The novel Pkc1 function is required for the expression of Cln2 G1 cyclin which leading to actin polarization polymerization which in turn leads to polar cell growth.
    (4)Growth regulation that involves calcineurin.
    We found that calcineurin and high osmolarity glycerol (HOG) pathway antagonize in the regulation of cell growth. More specifically, calcineurin is required for the inhibition of actin polarization at the bud site, and HOG pathway is required for the positive regulation of the formation of the bud after actin has polarized. This mechanism is required for the regulation of bud formation under the conditions of the changes in osmolarity of the environment.

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  • Regulation of the onset of mitosis

    Grant number：13043036

    2001 - 2005

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research on Priority Areas

    Awarding organization：Japan Society for the Promotion of Science

    HIRATA Dai

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    Grant amount：\37700000 （ Direct Cost: \37700000 ）

    Regulation of the onset of mitosis is important for checkpoint control and stress response. In this research, we studied a checkpoint monitoring cell polarity in fission and G2-M regulation by signaling pathways in budding yeast.
    Our findings are as follows.
    1. A checkpoint monitoring cell polarity in fission yeast
    (1) We showed that the fission yeast Funy-like protein Mor2 is required for cell polarity control and is localized to the cell ends and septum, and that the mor2 mutation disrupts the localization of F-actin, inducing a Weel-dependent G2-delay (EMBO J. 2002). Our results indicated that fission yeast cells have a novel checkpoint monitoring cell polarity. (2) We found that the conserved proteins, MO25-like Pmo25, GC kinase Nak1, Mor2, and NDR kinase Orb6, constitute a morphogenesis network (MOR) that is important for cell polarity and cell separation, and that the septation intiation network (SIN) regulates locaization of Pmo25 to SPB and the Nak1-Orb6 kinase activities during early interphase (EMBO J. 2005).
    2. G2-M regulation by signaling pathways in budding yeast :
    (1) We showed that the addition of ethanol causes Swe1-depdent G2 delay with a transient dispersion of F-actin cytoskeleton, resulting in an increase in cell size (Biosci. Biotechnol. Biochem. 2002). (2) We identified the SAH1 gene encoding S-adenosyl-L-homocysteine hydrolase as a mutation that suppressed the calcium-sensitive phenotypes of the zdsl-deleted cells, and showed that S-adenosylmethionine is involved in GI cell-cycle regulation (Proc. Nati. Acad. Sci. USA 2002). (3) We found antagonistic regulation of G2-M regulation and cell polarity control by the calcineurin and HOG-MAPK pathways (J. Biol. Chem. 2004). (4) We showed that Pkc1 is important for sustaining Cln2 level and polarized bud growth in response to calcium signal (J. Cell Sci. 2005).

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  • A novel checkpoint regulating the growth polarity in yeast

    Grant number：13680787

    2001 - 2003

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    HIRATA Dai

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    Grant amount：\3100000 （ Direct Cost: \3100000 ）

    Growth polarity and cell growth are coordinately regulated. To understand this mechanism, 1 studied a novel checkpoint regulating growth polarity in yeast. Research results are as follows.
    1.Fission yeast homologues of the B' subunit of PP2A plays critical roles in cell shape control and septum formation, and shares essential functions with calcineurin for viability.
    2.Fission yeast Wat1/Pop3 WD-repeat protein plays a role in genome stability and mRNA maturation.
    3.Budding yeast Isoleucyl-tRNA synthetase is identified as a target of the G1-specific inhibitor Reveromycin A.
    4.Fission yeast Mor2 is important for the localization of F-actin at the cell end(s) but not at the medial region, and is essential for the restriction of the growth zone(s) where Tip1 targets. Mor2 is homologous to the Drosophila Furry protein and is localized at both cell ends and the medial region of the cell in an actin-dependent fashion. Cellular localization of Mor2 and the Ndr kinase Orb6 was interdependent. The tyrosine kinase Wee1 is necessary for the G2 delay and maintenance of viability of the mor2 mutant. These results indicate that Mor2 plays as essential role in cell morphogonesis in concert. with Orb6, and the mutation activates the mechanism coordinating growth polarity with cell cycle progression.
    5.In budding east, calcineurin negatively regulates actin polarization at the bud site, whereas the HOG pathway positively regulates bud formation at a later step after actin has polarized.

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  • Screening of bio-active substances by using a peculiar phenotype of yeast mutant

    Grant number：11556017

    1999 - 2002

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    MIYAKAWA Tokichi, TAKAHASHI Hidetoshi, HIRATA Dai

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    Grant amount：\12300000 （ Direct Cost: \12300000 ）

    An inappropriate activation of a signaling pathway in yeast often has a deleterious physiological effect and causes various defects, including growth defects. In a certain genetic background (Δzdsl) of Saccharomyces cerevisiae, the cell-cycle progression in G2 is specifically blocked in the medium with CaCl_2 by the hyperactivation of the Ca^<2+>-signaling pathways. Here, we developed a novel drug screening procedure designed to detect the active compounds that specifically attenuate the Ca^<2+>-signaling activity on the basis of the ability to abrogate the growth defect of the cells suffering from the hyperactivated Ca^<2+> signal. Using known calcineurin inhibitors as model compounds, we have established the screening conditions for the drugs that suppress the Ca^<2+>-induced growth inhibition. An indicator strain with an increased drug sensitivity was constructed with a syr1/erg3 null mutation.

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  • Cooridinated Regulation of Cell morphogenesis and Crouth in Yeast

    Grant number：11680701

    1999 - 2000

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    HIRATA Dai

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    Grant amount：\3800000 （ Direct Cost: \3800000 ）

    Cell morphogenesis is closely regulated with cell proliferation. I studied the checkpoint mechanism of this coordination using budding and fission yeasts.
    1. Fission yeast α-glucan synthase Mok1 requires the actin cytoskeleton to localize the sites of growth and plays an essential role in cell morphogenesis downstream of protein kinase C function : We have isolated mok1^+ in a genetic screen to identify downstream effectors for Pck1/2. Mok1 has α-glucan synthase activity and plays a crucial role in cell morphogenesis.
    2. Functional dissection and hierarchy of tubulin-folding cofactor homologues in fission yeast : We identified fission yeast homologues of tubulin-folding cofactors B (Alp11) and E (Alp21).
    3. Overproduction of elongation factor 1α, an essential translational component, causes aberrant cell morphology by affecting the control of growth polarity in fission yeast : We showed that fission yeast EF1α has the ability to alter the morphology of yeast by affecting the control of actin and microtubule cytoskeletons.
    4. A positive screening for drugs that specifically inhibit the Ca^<2+>-signaling activity on the basis of the growth-promoting effect on a yeast mutant with a peculiar phenotype : We developed a novel drug screening procedure designed to detect the active compounds that inhibit the Ca^<2+>-signaling pathway.
    5. Regulation of Weel kinase in response to protein synthesis inhibition : Weel was essential for the G2 delay upon a partial inhibition of protein synthesis. Indeed, the protein synthesis inhibition caused an increase in the Weel protein by the Sty1 MAPK-dependent transcriptional and the Sty1 MAPK-independent post-transcriptional regulations.
    6. GSK-3 kinase Mck1 and calcineurin coordinately mediate Hsl1 down-regulation by Ca^<2+> in budding yeast : We identified Mck1 kinase, as a component of the Ca^<2+>-signaling pathway. Mck1 functions downstream of the Mpk1 pathway and down-regulate Hsl1 kinase.

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  • 酵母の多剤耐性における多様なABC蛋白の機能および発現制御ネットワーク

    Grant number：10217208

    1998 - 2002

    System name：科学研究費助成事業

    Research category：特定領域研究

    Awarding organization：日本学術振興会

    宮川 都吉, 平田 大

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    Grant amount：\36500000 （ Direct Cost: \36500000 ）

    ABCトランスポーターが構造的に関連性のない非常に広範な薬剤を認識して排出する機構は不明である。
    出芽酵母においてフルサイズのABCトランスポーターは約15種類存在するが、多剤耐性現象においては、Pdr5 ABCトランスポーターが圧倒的に重要な役割を果たしている。Pdr5は、極めて多種薬剤を認識して細胞外排出する。酵母のPdr5はABCトランスポーター機能解析の良いモデルと考えられる。そこで、特定薬剤に対する特異性を喪失した変異pdr5遺伝子を取得し、遺伝学的に解析し、Pdr5による薬剤認識の機構を解析した。PDR5遺伝子ORFをヒドロキシルアミン処理したプラスミドにより、pdr5破壊株を形質転換した。シクロヘキシイミド、スタウロスポリン、トリフルオペラジンまたはセルレニンを含む培地で各薬剤に対する薬剤耐性を試験し、調べた薬剤のいずれかの薬剤に感受性を示す株をその薬剤に対する感受性を失った変異と予想し選抜した。合計7各PDR5遺伝子の変異点をシークエンスにより決定し、各種薬剤に対する耐性、感受性の試験をした。変異点はORF全体に分散しており、各薬剤に特定の部位で対応しているのではなく、ABCトランスポーターの全体構造で対応している可能性が示唆された。

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  • Molecular analysis of cell cycle regulation by Ca^<2+>

    Grant number：10460044

    1998 - 2001

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    MIYAKAWA Tokichi, MIZUTA Keiko, HIRATA Dai

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    Grant amount：\12700000 （ Direct Cost: \12700000 ）

    We investigated molecular mechanism of G2/M cell cycle regulation by Ca^<2+> signal in Saccharomyces cerevisiae. We isolated mutants with a defect in the Ca^<2+> signaling pathway linked to cell cycle regulation. The mutants were classified to 14 complementation groups.
    (1) csz7 mutant was analyzed in detail. The scz7 mutation was identified as an allele of MCK1 that encodes a GSK-3 family protein kinase highly conserved among eukaryotes. It was found that Mck1 was involved in the Ca^<2+>-induced destabilization of Hsl1, Negative regulator of Swe1 through the ubiquitin-proteasome pathway. We further revealed the detailed mechanism by which Hsl1 abundance is regulated.
    (2) scz6 mutant was analyzed in detail. The scz6 mutation was identified as an allele of PKC1 that encodes a unique protein kinase C in the yeast. Interestingly, the scz6 mutation suppressed Ca^<2+> sensitive growth and Ca^<2+>-induced polarized bud growth, but not G2 cell cycle delay. We found a novel pathway of Pkc1, in which Pkc1 plays an important role in the regulation of the transcription of SWE1 And the G1 cyclin CLN1, in addition to the previously characterized pathway that activates the Mpk1 MAP kinase pathway. The transcription factor Swi4 was implicated in the transcriptional regulation of CLN1 and SWE1.
    scz5 mutant was analyzed in detail. The scz5 mutation was identified as an allele of PDR5 that encodes an ABC transporter implicated in multidrug resistance in the yeast. Pdr5 was suggested to be responsible for Ca^<2+> uptake.

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  • 酵母細胞を用いた細胞形態形成機構の分子遺伝学的解析

    Grant number：09760090

    1997 - 1998

    System name：科学研究費助成事業

    Research category：奨励研究(A)

    Awarding organization：日本学術振興会

    平田 大

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    Grant amount：\2500000 （ Direct Cost: \2500000 ）

    細胞形態形成は、細胞周期や分化機構と連動し、また細胞内外の多様な情報伝達系を介する複雑な機構である。多細胞においても、形態形成を制御する多様な情報の最終到達点は一細胞そのものであり、それゆえ多細胞の形態形成を理解する上で、単一細胞である酵母の形態形成機構の解明が必須であると考えた。そこで、多細胞生物と同様の細胞質分裂と極性成長様式をとる分裂酵母をモデル系として、形態形成機構の分子遺伝学的解析を行った。具体的には、以下の二つのアプローチにより研究を進めた。
    (1) 分裂酵母の細胞形態異常変異体の解析
    (1)極性方向異常変異体alpの解析から、微小管の新規な変異体alp2,12を同定した。これらはα-微小管因子とβ-微小管因子の変異であった。さらに、これらの変異が致死となる原因が、チェックポイント機構からの逸脱か、あるいはチェックポイント機構を十分に活性化できないためか、のいずれかの可能性があることを提示した。この解析から、微小管の構造維持や機能発現が、細胞増殖と形態形成に重要であることを示した。
    (2)極性方向異常変異体alpの解析から、細胞増殖および微小管重合に必須なAlp1を同定した。Alp1は、細胞周期をとおし、微小管に局在し、微小管の機能発現に重要であることを示した。
    (2) 過剰発現により細胞形態異常を示す遺伝子の解析
    過剰発現時に異常形態を示す遺伝子を系統的に分離したところ、低分子量GTP結合蛋白質Rho2を取得した。解析により、Rho2は極性成長領域に局在し、成長極性と細胞壁合成に重要であることを明らかにした。

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  • 酵母細胞を用いた形態形成機構の分子遺伝学的解析

    Grant number：08760088

    1996

    System name：科学研究費助成事業

    Research category：奨励研究(A)

    Awarding organization：日本学術振興会

    平田 大

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    Grant amount：\1000000 （ Direct Cost: \1000000 ）

    形態形成機構は、細胞周期や分化機構と連動した生物の基本的事象の一つである。形態形成は細胞内外の様々な情報によって制御される複雑な機構であるが、それら多様な情報の最終到達点は一細胞そのものであることから、多細胞における形態形成機構を理解する上で、単細胞での解析が必須であると考えた。そこで、高等動物と同様の細胞質分裂および極性成長様式をとり、その極性が細胞周期に依存してダイナミックに変化する分裂酵母(Schizosaccharomyces pombe)をモデル系として、形態形成機構の分子遺伝学的解析を行った。
    今回の研究から新規な形成形成関連分子を数種同定した。(1)成長極性が欠損している変異体の原因遺伝子sts5を同定した結果、形態形成との関連性が示唆されていなかった進化上高度に保存された分子が明らかになった。遺伝学的解析から、Sts5蛋白質は、細胞周期間期における成長極性の維持に必須な遺伝子であり、他のMAPキナーゼ情報伝達系と密接に機能関連していることが示唆された。(2)成長極性における対称性の維持に欠損をもつ変異体の原因遺伝子alp2を同定した結果、Alp2蛋白質は微小管構成分子であった。alp2変異体は成長極性のみならず、細胞内オルガネラの分配異常も示すことから、極性成長における対称性の維持機構に細胞骨格系蛋白質が重要な機能を担うことを明らかにした。今回得られた結果より、分裂酵母の形態形成関連分子の解析が、高等動物の細胞形態を理解する上で極めて重要であることが示唆された。

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  • Molecular mechanism of salt tolerance in yeast

    Grant number：07456050

    1995 - 1996

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    MIYAKAWA Tokichi, HIRATA Dai

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    Grant amount：\8200000 （ Direct Cost: \8200000 ）

    We investigated the mechanism for the maintenance of cation homeostasis in the yeast Saccharomyces cerevisiae. Followings are our findings.
    1.Salt tolerance mechanism that is regulated by calcineurin and protein kinase A :
    W have shown that the expression of ENA1 gene encoding a sodium extrusion pump ATPase which is responsible for decreasing salt concentrations under high salt environmentalconditions, is regulated positively by calcineurin and negatively by protein kinase A.
    2.Isolation and characterization of high-salt sensitive mutants :
    We isolated 1370 salt sensitive mutants, and classified the mutants to 30 complementation groups. Mutants that were suggested by genetic analysis to be defective in the functions that act downstream of calcineurin were selected (5 complementation groups). Genes that complement the defect of the mutant were isolated. Amongs the genes identified, a gene that encode putative transcription factor was found. The function of this gene in salt tolerance is under investigation.
    3.Isolation of muticopy suppressor genes that complement the defect of calcineurin-deficient mutant :
    Two each of the genes that encode putative transcription factor and putative membrane transporters were obtained by the screening. The function of these genes is under investigation by gene disruption experiment.

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  • 酵母のストレス応答におけるカルシニューリンの役割

    Grant number：05268227

    1993

    System name：科学研究費助成事業

    Research category：重点領域研究

    Awarding organization：日本学術振興会

    宮川 都吉, 平田 大

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    Grant amount：\2500000 （ Direct Cost: \2500000 ）

    酵母のCa^<2+>依存生プロテインホスファターゼ(カルシニューリン、PP2B)の触媒サブユニット(CMP1およびCMP2)、および調節サブユニット(CNB1)をコードする遺伝子を取得し、その生理機能を調べた。いずれも動物のPP2Bサブユニットに対し50%以上と高いアミノ酸同一性を有していたが、PP2Bサブユニットの破壊株はいずれも正常に増殖したことから、PP2Bは通常の増殖には必須でないことが明らかになった。しかし、PP2B破壊株は高NaCl、高LiCl、高pH培地およびバナジン酸を含む培地など細胞内イオンに影響するストレス下には生育不能であった。しかし、KCl,CaCl_2,MgCl_2を含む培地、および高濃度のソルビトールを含む高浸透圧培地での破壊株の生育は正常であったことから、一部のイオン(Na^+,Li^+およびH^+)に特異的な現象であることが明らかになった。高NaCl培地での細胞内Na^+およびK^+を測定した結果、培地の高NaClに抗して細胞内イオンの恒常性を維持するのにPP2Bが必須の役割を果していることが分かった。これらのストレス適応は免疫抑制剤(FK506やCyclosporin A)に感受性で、免疫抑制剤の結果は、対応するイムノフィリン(それぞれFKBP-12およびcyclophilin)依存的であった。免疫抑制剤存在下の細胞内イオンの動向はPP2B破壊株の場合と同様であった。

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  • Coordinated Regulation of Morphogenesis and Cell growth

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    Grant type：Competitive

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  • 形態形成と細胞増殖との連携制御機構

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    Grant type：Competitive

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Teaching Experience (researchmap)

Teaching Experience

  • 食品科学プログラム実地見学

    2025
    Institution name：新潟大学

  • スタディ・スキルズAIa

    2024
    Institution name：新潟大学

  • スタディ・スキルズAIIa

    2024
    Institution name：新潟大学

  • 日本酒学特論II

    2023
    Institution name：新潟大学

  • 日本酒学博士セミナーIII

    2023
    Institution name：新潟大学

  • 日本酒学国際特別研究

    2023
    Institution name：新潟大学

  • 日本酒学特論I

    2023
    Institution name：新潟大学

  • 課題発掘・解決セミナーII

    2023
    Institution name：新潟大学

  • 日本酒学博士セミナーII

    2023
    Institution name：新潟大学

  • 日本酒学博士セミナーI

    2023
    Institution name：新潟大学

  • 日本酒学概論V(医歯学・保健学)

    2023
    Institution name：新潟大学

  • 農学入門I

    2023
    Institution name：新潟大学

  • 農学入門II

    2023
    Institution name：新潟大学

  • 日本酒学概論I(自然科学)

    2022
    Institution name：新潟大学

  • 発展日本酒学実習

    2022
    Institution name：新潟大学

  • 日本酒学A

    2022
    Institution name：新潟大学

  • 日本酒学概論III(人文社会科学)

    2022
    Institution name：新潟大学

  • 日本酒学概論II(自然科学)

    2022
    Institution name：新潟大学

  • 課題発掘・解決セミナーI

    2022
    Institution name：新潟大学

  • 基礎日本酒学実習

    2022
    Institution name：新潟大学

  • 日本酒学概論IV(人文社会科学)

    2022
    Institution name：新潟大学

  • 応用生命・食品科学概論

    2022
    Institution name：新潟大学

  • スタディ・スキルズAIb

    2022
    Institution name：新潟大学

  • Topics in Biotechnology and Biochemistry

    2022
    Institution name：新潟大学

  • スタディ・スキルズAIIb

    2022
    Institution name：新潟大学

  • 日本酒学A-1

    2021
    Institution name：新潟大学

  • 醸造学特論II

    2021
    Institution name：新潟大学

  • 日本酒学A-2

    2021
    Institution name：新潟大学

  • 醸造学特論I

    2021
    Institution name：新潟大学

  • 応用生命・食品科学セミナーI

    2021
    Institution name：新潟大学

  • 食と健康の科学

    2020
    Institution name：新潟大学

  • 食品科学概論

    2020
    Institution name：新潟大学

  • 生命を知る

    2020
    Institution name：新潟大学

  • 微生物学実験

    2020
    Institution name：新潟大学

  • 醸造学

    2020
    Institution name：新潟大学

  • 日本酒学B

    2020
    Institution name：新潟大学

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