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Regulatory Mechanism of M-phase by MPF,M-phase Promoting Factor

Research Project

Project/Area Number 03405004
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field 広領域
Research InstitutionTokyo Institute of Technology

Principal Investigator

KISHIMOTO Takeo  Tokyo Institute of Technology, Faculty of Bioscience and Biotechnology, Professor, 生命理工学部, 教授 (00124222)

Co-Investigator(Kenkyū-buntansha) 大隈 圭太  東京工業大学, 生命理工学部, 助手 (20221822)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥21,900,000 (Direct Cost: ¥21,900,000)
Fiscal Year 1993: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1992: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 1991: ¥15,800,000 (Direct Cost: ¥15,800,000)
KeywordsM-phase / MPF / cdc2 kinase / cdc2 / cyclin B complex / sucl-affinity chromatography / nuclear transport / chromosome condensation / mitotic apparatus / ヒストンH1 / ヒトデ卵 / アフリカツメガエル卵 / 微小管 / 中間径繊維 / MAP / suc1産物 / ビメンチンキナーゼ / MTOC / suc1遺伝子
Research Abstract

MPF (M-phase promoting factor), which is composed of the p34^<cdc2>/cyclin B complex, cdc2 kinase, governs M-phase in all eukaryotic cells. In this project, we studied how M-phase is executed by cdc2 kinase, and obtained following results.
1.We developed a new method to purify cdc2 kinase at high performance by modifying p13^<sucl>-affinity chromatography. This enabled us to analyze the function of cdc2 kinase in inducing various M-phase events.
2.At G2/M-phase border, the inactive form of p34^<cdc2>/cyclin B complex localizes in the cytoplasm. The complex is transformed to active form in the cytoplasm at the transition to M-phase. Thereafter, a part of the complex moves into nucleus, while other associates with mitotic apparatus. These specific localizations of the complex might support its specific function to execute M-phase within a cell.
3.In contrast to the previous belief that histone H1 phosphorylation by cdc2 kinase plays a key role in chromosome condensation, condensation occurs normally even in the chromatins lacking histone H1. This suggests the presence of an unknown major target of cdc2 kinase for chromosome condensation other than histone H1.
4.The p34^<cdc2/>cyclin B complex associates with a microtubule via the binding between cyclin B component and the prolin-rich region of MAP4. In such a complex, cdc2 kinase phosphorylates MAP4 to decrease its microtubule-stabilizing ability, resulting in increased dynamic instability of an individual microtubule. This effect of cdc2 kinase appears to contribute to form metaphase spindle.

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (41 results)

All Other

All Publications (41 results)

  • [Publications] Hisanaga,S.,et al.: "Phosphorylation of neurofilament H subunit at the tail domain by CDC2..." J.Biol.Chem.266. 21798-21803 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ookata,K.,et al.: "Relocation and distinct subcellular localization of p34^<cdc2> -cyclin B...." EMBO J.11. 1763-1772 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ookata,K.,et al.: "Association of p34 ^<cdc2>/cyclin B complex with microtubules in starfish oocytes." J.Cell Sci.105. 873-881 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ohsumi,K.,et al.: "Chromosome condensation in Xenopus mitotic extracts without histone Hl." Science. 262. 2033-2035 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kishimoto,T.: "Cell reproduction ; induction of M-phase events by cyclin-dependent cdc2 kinase." Int.J.Dev.Biol.38. 185-191 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ookata,K.,et al.: "Cyclin B interaction with microtubule-associated protein 4 (MAP4) targets...." J.Cell Biol.128. 849-862 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 岸本健雄(分担): "新生化学実験講座 vol.14,「発生・分化・老化」(今堀和友、堀田凱樹、近藤寿人、永井克孝編)" 東京化学同人, 541 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 岸本健雄(分担): "最新・細胞周期ライブラリー(田矢洋一、野島博、花岡文雄編)" 羊土社(印刷中), (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hisanaga, S., Kusubata, M.Okumura, E., and Kishimoto, T.: "Phosphorylation of neurofilament H subunit at the tail domain by CDC2 kinase dissociates the association to microtubules." J.Biol.Chem. 266. 21798-21803 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ookata, K., Hisanaga, S., Okano, T., Tachibana, K., and Kishimoto, T.: "Relocation and distinct subcellular localization of p34^<cdc2>-cyclin B complex at meiosis reinitiation in starfish oocytes." EMBO J.11. 1763-1772 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kusubata, M.Tokui, T., Matsuoka, Y., Okumura, E., Tachibana, K., Hisanaga, S., Kishimoto, T., Yasuda, H., Kamijo, M., Ohba, T., Tsujimura, K., Yatani, R., and Inagaki, M.: "P13^<sucl> suppresses the catalytic function of p34^<cdc2> kinase for intermediate filament proteins, in vitro." J.Biol.Chem.267. 20937-20942 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hisanaga, s., Ishiguro, K., Uchida, T., Okumura, E., Okano, T., and Kishimoto, T.: "Tau protein kinase II has a similar characteristic to cdc2 kinase for phosphorylating neurofilament proteins." J.Biol.Chem.268. 15056-15060 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ookata, K., Hisanaga, S., Okumura, E., and Kishimoto, T.: "Association of p34^<cdc2>/cyclin B complex with microtubules in starfish oocytes." J.Cell Sci.105. 873-881 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ohsumi, K., Katagiri, Ch., and Kishimoto, T.: "Chromosome condensation in Xenopus mitotic extracts without histone H1." Science. 262. 2033-2035 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kishimoto, T.: "Cell reproductio : induction of M-phase events by cyclin-dependent cdc2 kinase." Int.J.Dev.Biol.38. 185-191 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ohsumi, K., Sawada, W., and Kishimoto, T.: "Meiosisspecific Cell cycle regulation in maturing Xenopus oocyte." J.Cell Sci.107. 3005-3013 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ookata, K., Hisanaga, S., Bulinski, J.C., Murofushi, H., Aizawa, H., Itoh, T.J., Hotani, H., Okumura, E., Tachibana, K., and Kishimoto, T.: "Cyclin B interaction with microtubule-associated protein 4 (MAP4) targets p34^<cdc2> kinase to microtubules and is a potential regulator of M-phase microtubule dynamics." J.Cell Biol.128. 849-862 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hisanaga, S., Uchiyama, M., Hosoi, T., Yamada, K., Honma, N., Ishiguro, K., Uchida, T., Dahl, D., Ohsumi, K., and Kishimoto, T.: "Procine brain neurofilament-H tail domain kinase : its identification as CDK5/p26 complex, and comparison with CDC2/cyclin B kinase." Cell Motil. Cytoskel.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ohta,K.,et al.: "Microtubule nucleating activity of centrosomes in cell-free extracts from Xenopus eggs:Involvement...." J.Cell Sci.104. 125-137 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hisanaga,S.,et al.: "Tau protein kinase II has a similar characteristic to cdc2 kinase for phosphorylating neurofilament proteins." J.Biol.Chem.268. 15056-15060 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ando,S.,et al.: "Phosphorylation of synthetic vimentin peptides by cdc2 kinase." Biochem.Biophys.Res.Commun.195. 837-843 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ookata,K.,et al.: "Association of p34^<cdc2>/cyclin B complex with microtubules in starfish oocytes." J.Cell Sci.105. 873-881 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ohsumi,K.et al.: "Chromosome condensation in Xenopus mitotic extracts without histone H1." Science. 262. 2033-2035 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 岸本健雄: "細胞周期" 生体の科学. 44. 442-445 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kishimoto,T.(分担): "Biology of the germ line-In animals and man." Japan Scientific Societies Press(Tokyo)(Mohri,H.,Takahashi,M.and Tachi,C.,eds.), 304 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ookata,K.,et al.: "Relocation and distinct subcellular localization of p34 cdc2-cyclin B complex at meiosis reinitiation in starfish oocytes." EMBO J.11. 1763-1772 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kusubata,M.,et al.: "P13 suc1 suppresses the catalvtic function of p34 cdc2 kinase for intermediate filament proteins,in vitro." J.Biol.Chem.267. 20937-20942 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Ohta,K.,et al.: "Microtubule nucleating activity of centrosomes in cell-free extracts arom Xenopus eggs." J.Cell Sci.104. 125-137 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kusubata,M.,et al.: "cdc2 kinase phosphorylation of desmin at three serine/threonine residues in the amino-terminal head domain." Biochem.Biophys.Res.Commun.(1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hisanaga,S.,et al.: "Dephosphorylation of microtubule-binding sites at the neurofilament-H tail domain by alkaline,acid and protein phosphatases." J.Biochem.(1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hisanaga,S.,et al.: "Tau protein kinase II has a similar characteristic to cdc2 kinase for phosporylating neurofilament proteins." J.Biol.Chem.(1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 岸本 健雄(今堀 和友他編): "卵成熟とcdc2キナーゼ(新生化学実験講座、第14巻「発生・分化・老化」)" 東京化学同人, 550 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kishimoto,T.(eds.H.Mohre,M.Takahashi and C.Tachi): "Control of M-Phase by MPF/cyclin-dependent cdc2 kinase.(In “Biology of germ lines-in animals and man-)" 学会出版センター, (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Gotoh,Y.: "Xenopus M phase MAP Kinase:isolation of its cDNA and activation by MPF." EMBO J.10. 2661-2668 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hisanaga,S.: "Phosphorylation of neurofilament H subunit at the tail domain by cdc2 Kinase dissociates the association to microtubules." J.Biol.Chem.266. 21798-21803 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] OoKata,K: "Relcation and distinct subcellular localization of p34 cdc2/cyclin B complex at meiosis reinitiation in starfish oocytes." EMBO J.11. 5 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ohta,K.: "Increase of microtubule nucleating activity of centrosome in cellーfree extracts from Xenopus eggs and its regulation by protein phosphorylation." Proc.Natl.Acad.Sci.USA.89. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 立花 和則: "cdc2キナ-ゼによる細胞周期の制御" 実験医学. 9. 1640-1648 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 岸本 健雄: "MPF・cdc2キナ-ゼ・サイクリンーM期の制御と細胞周期の制御ー" Annual Review 細胞生物学1991. 1. 217-235 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kishimoto,T.: "Control of Mーphase by MPF/cyclinーdependent cdc2 kinase.in“Biology of germ linesーin animals and manー"(eds.H.Mohri,M.Takahashi and C.Tachi)" 学会出版センタ-, (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 岸本 健雄: "卵成卵とcdc2キナ-ゼ(新生化学実験講座(日本生化学会編)第14巻「発生、分化および老化」)" 東京化学同人, (1992)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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