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Threshold-setting for activation of cyclin B-Cdk1 at meiotic G2/M-phase transition in oocytes

Research Project

Project/Area Number 16H04783
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionOchanomizu University

Principal Investigator

Kishimoto Takeo  お茶の水女子大学, サイエンス&エデュケーションセンター, 客員教授 (00124222)

Co-Investigator(Kenkyū-buntansha) 奥村 英一  東京工業大学, 生命理工学院, 助教 (00323808)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2016: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywordsシグナル伝達 / 細胞周期 / G2/M期移行 / cyclin B-Cdk1 / 卵細胞 / cycylin B-Cdk1
Outline of Final Research Achievements

Meiotic cell cycle progression in oocytes is characterized by its link with extracellular stimuli. Here, we investigated the mechanism for threshold establishment in activation of cyclin B-Cdk1, a universal inducer of M-phase, after maturation-inducing hormonal stimulus. Our results indicate the presence of triple barrier against cyclin B-Cdk1 activation: first, constitutively active phosphatase that counteracts phosphorylation by a trigger kinase for initial activation of cyclin B-Cdk1; second, noise-cancelling through negative feedback that depends on partially activated cyclin B-Cdk1 after subthreshold hormonal stimulus; and third, start of autoregulatory activation of cyclin B-Cdk1 through positive feedback that depends on initially activated cyclin B-Cdk1. We propose that hormonal dose-dependent competition with these barriers establishes a threshold.

Academic Significance and Societal Importance of the Research Achievements

本研究では、細胞分裂期の開始を決定する(decision-making)分子メカニズムの一端を明らかにした。実験材料にはヒトデ卵を用いているが、そこから得られた知見は、ヒトも含めた全真核生物にインパクトを及ぼすものである。純粋な基礎科学としての研究ではあるが、細胞分裂期および卵細胞を対象としていることから、その成果は、がんなどの異常な細胞増殖とともに卵細胞に起因する不妊の原因を探り、対策を講じる手掛かりとなるものでもある。

Report

(4 results)
  • 2019 Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (15 results)

All 2020 2019 2018 2017 2016 Other

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (6 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Book (1 results) Remarks (2 results)

  • [Journal Article] SGK phosphorylates Cdc25 and Myt1 to trigger cyclin B-Cdk1 activation at the meiotic G2/M transition2019

    • Author(s)
      Hiraoka, D., Hosoda, E., Chiba, K., and Kishimoto
    • Journal Title

      J Cell Biol.

      Volume: 218 Issue: 11 Pages: 3597-3611

    • DOI

      10.1083/jcb.201812122

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SGK regulates pH increase and cyclin B-Cdk1 activation to resume meiosis in starfish ovarian oocytes.2019

    • Author(s)
      Hosoda, E., Hiraoka, D., Hirohashi, N., Omi, S., Kishimoto, T. and Chiba, K.
    • Journal Title

      J Cell Biol.

      Volume: 218 Issue: 11 Pages: 3612-3629

    • DOI

      10.1083/jcb.201812133

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MPF-based meiotic cell cycle control: Half a century of lessons from starfish oocytes2018

    • Author(s)
      KISHIMOTO Takeo
    • Journal Title

      Proceedings of the Japan Academy, Series B

      Volume: 94 Issue: 4 Pages: 180-203

    • DOI

      10.2183/pjab.94.013

    • NAID

      130006691115

    • ISSN
      0386-2208, 1349-2896
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of jellyfish neuropeptides that act directly as oocyte maturation-inducing hormones2018

    • Author(s)
      Takeda, N., Kon, Y., Quiroga Artigas, G., Lapebie, P., Barreau, C., Koizumi, O., Kishimoto, T., Tachibana, K., Houliston, E., Deguchi, R.
    • Journal Title

      Development

      Volume: 145 Issue: 2

    • DOI

      10.1242/dev.156786

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Two new competing pathways establish the threshold for cyclin B-Cdk1 activation at the meiotic G2/M transition.2016

    • Author(s)
      Hiraoka, D., Aono, R., Hanada, S., Okumura, E., and Kishimoto, T.
    • Journal Title

      J. Cell Sci.

      Volume: 129 Pages: 3153-3166

    • DOI

      10.1242/jcs.182170

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] MPF, starfish oocyte and cell-free extract in the background - an interview with Takeo Kishimoto.2016

    • Author(s)
      Kubiak, J.Z., and Kishimoto, T.
    • Journal Title

      Int. J. Dev. Biol.

      Volume: 60 Issue: 7-8-9 Pages: 193-200

    • DOI

      10.1387/ijdb.160348jk

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] In commemoration of the half-centennial anniversary: 1-Methyladenine identification in starfish oocytes and beyond2019

    • Author(s)
      Takeo Kishimoto
    • Organizer
      International Oocyte Meeting V (Villefranche-Sur-Mer, France)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 1-メチルアデニンに始まる卵細胞周期制御の解明2019

    • Author(s)
      岸本健雄
    • Organizer
      日本動物学会第90回大阪大会シンポジウム「ヒトデ卵成熟誘起ホルモン1-メチルアデニンの同定50周年記念シンポジウム」
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 1-メチルアデニンが切り開いた卵細胞周期の制御機構に関する研究2017

    • Author(s)
      岸本健雄
    • Organizer
      日本動物学会第88回富山大会シンポジウム「ヒトデの生殖生物学ー1-メチルアデニンの発見から半世紀」
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] PI3KとGbg依存的な新規経路の協調的な働きによるヒトデ卵減数分裂再開の分子機構2017

    • Author(s)
      平岡大作、細田絵奈子、千葉和義、岸本健雄
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Serum glucocorticoid-regulated kinase (SGK)はヒトデ卵母細胞の細胞内pH上昇の促進と卵成熟の誘起に関与する2017

    • Author(s)
      細田絵奈子、平岡大作、福田絵里子、尾見早紀、広橋敬貴、岸本健雄、千葉和義
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] サイクリンB-Cdk1はAktの基質を標的とする脱リン酸化酵素の活性化により、減数分裂再開の閾値設定に関わる負のフィードバックをもたらす.2016

    • Author(s)
      平岡大作、岸本健雄
    • Organizer
      第39回日本分子生物学会年会
    • Related Report
      2016 Annual Research Report
  • [Book] Methods in Molecular Biology "Developmental Biology of the Sea Urchin and Other Marine Invertebrates: Methods and Protocols, Second Edition" (eds. Stephen A. Stricker and David J. Carroll)2020

    • Author(s)
      Murabe, N., Okumura, E., Chiba, K., Hosoda, E., Ikegami, S., and Kishimoto, T.
    • Publisher
      Springer Science+Business Media, New York
    • Related Report
      2018 Annual Research Report
  • [Remarks] お茶の水女子大学 サイエンス&エデュケーションセンター 岸本健雄客員教授

    • URL

      http://www.cf.ocha.ac.jp/sec/kishimoto/profile.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] お茶の水女子大学 サイエンス&エデュケーションセンター 岸本健雄客員教授 岸本研究グループ

    • URL

      http://www.cf.ocha.ac.jp/sec/kishimoto/profile.html

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report

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Published: 2016-04-21   Modified: 2021-02-19  

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