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2007 Fiscal Year Final Research Report Summary

Basic and Applied Research on tie Roles of Ca^<2+>-Signal-mediated Cell-Cycle Regulation in Budding Yeast.

Research Project

Project/Area Number 17208009
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied biochemistry
Research InstitutionHiroshima University

Principal Investigator

MIYAKAWA Tokichi  Hiroshima University, Graduate School of Advanced Sciences of Matter, Professor (10116676)

Co-Investigator(Kenkyū-buntansha) KADOTA Shigetoshi  Toyama Univ., Wakanyaku Inst, Professor (90115163)
Project Period (FY) 2005 – 2007
KeywordsSaccharomvces cerevisiae / Ca^<2+> sienal transduction / Calcineurin / Cell cycle regulation / S-adenosvl methionine / HOG pathway / Cell cycle checknoint / Protein kinase C
Research Abstract

Analyses of cell-cycle regulation and investigation of its physiological role For understanding detailed mechanism for the Ca^<2+>-signal mediated cell-cycle regulation in yeast, we isolated mutants (designated scz) defective in this process and performed molecular genetic analyses of the mutants.
(1) By the analysis of scz6 mutation, we found that the phenotype is caused by a mutation of PKC1 gene. We further demonstrated that C-kinase and A-kinase antagonistically regulates Cln2, and thereby regulate cell growth and polarized bud growth, suggesting a crosstalk between A-kinase and C-kinase pathways.
(2) By the analysis of sczl3 mutation, we found a mutation of Alg9 which is involved in the protein N-glycosylation in the ER lumen is responsible for suppression of the Ca^<2+> phenotype. We found that N-glycosylation of proteins is important for the maintenance of Swel and Cln2 levels.
We also developed a procedure to detect bioactive compounds which inhibit Ca^<2+>-signal mediated cell-cycle regulation and screened for active substances from various sources. We investigated action mechanisms of two small-molecule compounds found by the screening.
(1) Radicicol, inhibitor of Hsp90, inhibits Ca^<2+>-signal mediated cell-cycle regulation by destabilizing Swel, inhibitory Idnase of Cdc28/Clb.
(2) By molecular genetic analysis of the mutants resistant to NKH-7, we identified Tubl α-tubulin as target of this compound. Based on its physiological effect and mutation site of Tub I, we suggested that NKH-7 destabilizes microtubules by binding to Tubl α-tubulin.

  • Research Products

    (29 results)

All 2008 2007 2006 2005

All Journal Article (24 results) (of which Peer Reviewed: 11 results) Book (2 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] Identification of Saccharomyces cerevisiae Tub1 α-tubulin as a potential target for NKH-7, a cytotoxic 1-naphthol derivative compound.2008

    • Author(s)
      R. Chanklan,
    • Journal Title

      Biosci. Biotechnol. Biochem. 72(印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Inhibition of Ca^<2+>-signal-dependent growth regulation by radicicol in budding yeast.2008

    • Author(s)
      R. Chanklan,
    • Journal Title

      Biosci. Biotechnol. Biochem. 72

      Pages: 132-138

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Identification of Tup1 and Cyc8 mutations defective in the responses to osmotic stress2008

    • Author(s)
      Y. Kobayashi,
    • Journal Title

      Biochem. Biophys. Res. Commun., 368

      Pages: 50-55

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Identification of Tubl a-Tubulin as a Potential Target for NKH-7, a cytotoxic 1-Naphthol Derivative Compound2008

    • Author(s)
      R., Chanklan, M., Mizunuma, N., Kongkathip, K., Hasitapan, B., Kongkathip, T., Miyakawa
    • Journal Title

      Biosel Biotechnol Biochem 72(in Press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Identification of Tupl and Cyc8 mutations defective in the responses to osmotic stress2008

    • Author(s)
      Y., Kobayashi, T., Thai, M., Mizunuma, I., Okada, A., Shitamukai, D., Hirata, T., Miyakawa
    • Journal Title

      Biochem. Biophys. Res. Commun 368

      Pages: 50-55

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Inhibition of Ca^<2+>-signal-sependent growth regulation by eadicicol in budding yeast2008

    • Author(s)
      R., Chanklan, E., Aihara, S., Koga, H., Takahashi, M., Mizunuma, T., Miyakawa
    • Journal Title

      Biosci, Biotechnol. Biochem 72

      Pages: 132-138

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Physiological roles of calcineurin in Saccharomyces cerevisiae with special emphasis on its roles in G_2/M cell- cycle regulation.2007

    • Author(s)
      T, Miyakawa
    • Journal Title

      Biosci. Biotechnol. Biochem. 71

      Pages: 633-645

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] YCM1008A, a novel Ca^<2+>-signaling inhibitor, produced by Fusarium sp. YCM10082007

    • Author(s)
      F, Koizumi,
    • Journal Title

      J. Antibiotics 60

      Pages: 455-458

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] YCM1008A, a novel Ca^<2+>-signaling inhibitor, produced by Fusarium sp.YCM10082007

    • Author(s)
      F., Koizumi, N., Fukumitsu, J., Zhao, R., Chanklan, T., Miyakawa, S., Kawahara, S., Iwamoto, M., Suzuki, S., Kakita, E.S., Rahayu, S., Hosokawa, K., Tatsuta, M., Ichimura
    • Journal Title

      J Antibiotics 60

      Pages: 455-458

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Physiological roles of calcineurin in Saccharomyces cerevisiae with special emphasis on its roles in G2/M call-cycle regulation2007

    • Author(s)
      T., Miyakawa, M., Mizunuma
    • Journal Title

      Biosci Biotechnol Biocbem 71

      Pages: 633-645

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Involvement of Yaplp downregulation in calcineurin-mediated G2 cell-cycle regulation in Saccharomyces cerevisiae.2006

    • Author(s)
      H. Yokoyama,
    • Journal Title

      EMBO reports 7

      Pages: 519-524

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Identification of Saccharomyces cerevisiae Ribosomal Protein L3 as a Target of Curvularol, a G_1-Specific Inhibitor of Mammalian Cells2006

    • Author(s)
      Y. Kobayashi,
    • Journal Title

      Biosci. Biotechnol. Biochem. 70

      Pages: 2451-2459

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] 酵母でスクリーニングされた植物由来のCa^<2+>シグナル伝達阻害物質2006

    • Author(s)
      木村賢一、
    • Journal Title

      バイオサイエンスとバイオインダストリー 64

      Pages: 214-218

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Ca^<2+>シグナルによる酵母の細胞周期制御 機構解明と医薬シーズ探索への応用2006

    • Author(s)
      宮川都吉、
    • Journal Title

      バイオサイエンスとバイオインダストリー 64

      Pages: 373-378

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Involvement of Yaplp downregulation in calcineurin-mediated G2 cell-cycle regulation in Saccharomyces cerevisiae2006

    • Author(s)
      H., Yokoyama, M., Mizunuma, M., Okamoto, D., Hirata, T., Miyakawa
    • Journal Title

      EMBO reports 7

      Pages: 519-524

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Identification of Saccharomyces cerevisiae Ribosomal Protein L3 as a Target of Curvularol, a G_1-Specific Inhibitor of Mammalian Cells2006

    • Author(s)
      Y., Kobayashi, M., Mizunuma, H., Osada, T., Miyakawa
    • Journal Title

      Biosci, Biotechnol. Biochem 70

      Pages: 2451-2459

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Implication of Pkc1p protein kinase C in sustaining Cln2p level and polarized bud growth in response to calcium signaling in Saccharomyces cerevisiae.2005

    • Author(s)
      M. Mizunuma,
    • Journal Title

      J. Cell Sci. 118

      Pages: 4219-4229

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Mutational analysis of the yeast multidrug resistance ABC transporter Pdr5p with altered drug specificity2005

    • Author(s)
      A.C. Tutulan-Cunita,
    • Journal Title

      Gene Cells 10

      Pages: 409-420

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Involvement of Saccharomyces cerevisiae Pdr5p ATP-binding cassette Transporter in calcium homeostasis2005

    • Author(s)
      A.C. Tutulan-Cunita,
    • Journal Title

      Biosci. Biotechnol. Biochem. 69

      Pages: 857-860

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Role of L-histidine in conferring tolerance to Ni^<2÷> in Saccharomyces cerevisiae2005

    • Author(s)
      I., C. Farcasanu,
    • Journal Title

      Biosci. Biotechnol. Biochem. 69

      Pages: 2343-2348

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Implication of Pkelp protein Kinase C in sustaining Cln2p level and polarized bud growth in response to calcium signaling in Saccharonryces cerevisiae2005

    • Author(s)
      M., Mizunuma, D., Hirata, T., Miyakawa
    • Journal Title

      J. Cell Scl 118

      Pages: 4219-4229

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Mutational analysis of the yeast multidrug resistance ABC transporter Pdr5p with altered drug specificity2005

    • Author(s)
      A.C., Tutulan-Cunita, M.o., Mikoshi, M., Mizunurna, D., Himta, T., Miyakawa
    • Journal Title

      Gene Cells 10

      Pages: 409-420

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Involvement of Saccharomyces cerevisiae Pdr5p ATP-binding cassette Transporter in calcium homeostasis2005

    • Author(s)
      A.C., Tutulan-Cunita, T., Ohnishi, M., Mizunuma, D., Hirata, T., Miyakawa
    • Journal Title

      Biosci. Biotechnol. Biochem 69

      Pages: 857-860

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Role of L-histidine in conferring tolerance to Ni^<2+> in Saccharomyces cerevisiae2005

    • Author(s)
      L.C., Farcasanu, M., Mizunuma, F., Nishiyama, T., Miyakawa
    • Journal Title

      Biosci. Biotechnol. Biochem 69

      Pages: 2343-2348

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] 蛋白質核酸酵素 酵母による低分子阻害物質標的蛋白質の同定2007

    • Author(s)
      宮川都吉
    • Total Pages
      5
    • Publisher
      共立出版
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 酵母のすべてストレス応答性MAPキナーゼ経路とCa^<2÷>シグナル伝達2007

    • Author(s)
      宮川都吉
    • Total Pages
      7
    • Publisher
      シュプリンガー・ジャパン
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] 微小管重合阻害化合物、およびその利用2008

    • Inventor(s)
      宮川都吉, 他
    • Industrial Property Rights Holder
      広島大学, カセサート大
    • Industrial Property Number
      特願2008-026621
    • Filing Date
      2008-02-06
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] アンスラコビア酸化合物、その医薬用途、その取得方法および取得に有用な菌株2008

    • Inventor(s)
      塩野義人, 他
    • Industrial Property Rights Holder
      山形大学, 岩手大学, 広島大学
    • Industrial Property Number
      特願2006-016864
    • Filing Date
      2008-02-06
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] 2H-ピラノ[3, 2-c]ピリジン-5(6H)-オン誘導体2007

    • Inventor(s)
      宮川都吉, 他
    • Industrial Property Rights Holder
      広島大学, 他
    • Industrial Property Number
      特願2007-048434
    • Filing Date
      2007-02-28
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2010-02-04  

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