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Wee1Bを介した哺乳動物卵母細胞減数分裂機構とその異常

Research Project

Project/Area Number 20659260
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Obstetrics and gynecology
Research InstitutionNagoya City University

Principal Investigator

中西 真  Nagoya City University, 大学院・医学研究科, 教授 (40217774)

Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2008: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywords減数分裂 / 細胞周期 / 不妊
Research Abstract

卵母細胞の減数分裂異常は、不妊あるいは胎児の染色体異常等の原因となると考えられているが、その詳細な分子機構については全く分かっていない。本研究は、哺乳動物細胞における減数分裂機構の解明と、その不全による不妊等の病態解明を目指して、マウス卵母における減数分裂の進行を制御する新たな因子の同定と、その機能解析を目指して行われた。申請者らは、マウス細胞から世界に先駆けて卵母細胞特異的な細胞周期進行因子、Wee1Bを同定してその機能解析を行った。Wee1BはサイクリンB-Cdk1複合体のCdk1分子のチロシン15を特異的にリン酸化することが分かった。このマウスWee1B分子を分裂酵母Wee1変異株に導入してWee表現型の相補能について解析を行ったところ、分裂酵母Wee1の機能を完全に相補することが分かった。この結果は、Wee1BによるCdk1分子のチロシン15のリン酸化は減数分裂の進行を負に制御することを示している。さらに、マウス卵母細胞成熟時におけるWee1Bタンパク質の挙動を解析したところ、第一減数分裂複製期よりWee1Bタンパク質のリン酸化が認められ、第一減数分裂M期にかけてこのリン酸化が維持されることが分かった。これらの成果は哺乳動物細胞においてWee1Bタンパク質は減数分裂の進行に必須の役割を果たしていることを強く示唆していると考えられる。今後Wee1B遺伝子の変異について不妊患者さんのサンプルを用いて解析していく予定である。

Report

(2 results)
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (18 results)

All 2010 2009 2008

All Journal Article (14 results) (of which Peer Reviewed: 14 results) Presentation (3 results) Book (1 results)

  • [Journal Article] Essential role of Tip60-dependent recruitment of ribonucleotide reductase at DNA damage sites in DNA repair during G1 phase2010

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

      Genes and Dev. 24

      Pages: 333-338

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anaphase promoting complex/cyclosome-cdh1 mediates the ubiquitination and degradation of TRB32010

    • Author(s)
      Ohoka, N.
    • Journal Title

      Biochem.Biophys.Res.Commun. 18

      Pages: 103-113

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of origin firing program in mammals through Chk1-cyclin A/Cdk1 axis2010

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

      Chromosomal Res. 18

      Pages: 103-113

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DNA damage responses in skin biology-Implications in tumor prevention and aging acceleration2009

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

      J Dermatol Sci. 56

      Pages: 333-338

    • NAID

      10025560903

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Casein kinase II is required for the spindle assembly check point by regulating Mad2p in fission yeast2009

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

      Biochem.Biophys.Res.Commun. 388

      Pages: 529-532

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ptpcd-1 is a novel cell cycle related phosphatase that regulates centriole duplication and cytokinesis2009

    • Author(s)
      Zineldeen, D.H.
    • Journal Title

      Biochem.Biophys.Res.Commun. 380

      Pages: 460-466

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ptpcd-1 is a novel cell cycle related phosphatase that regulates centriole duplication and cytokinesis.2009

    • Author(s)
      Zineldeen, D. H.
    • Journal Title

      Biocbem. Biophys. Res. Commun. 380

      Pages: 460-466

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Disruption of the novel gene fad 14 causes rapid postnatal death and attenuation of cell proliferation, adhesion, spreading and migration.2009

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

      Exp. Cell Res. 315

      Pages: 809-819

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cyclin A-Cdk1 regulates the origin firing program in mammalian cells.2009

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

      Proc. Nat1. Acad. Sei. 106

      Pages: 3184-3189

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Peroxisome proliferator-activated receptor-gamma and growth inhibition by its ligands in prostate cancer.2008

    • Author(s)
      Nagata, D.
    • Journal Title

      Cancer Detect Prev. 32

      Pages: 259-266

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Essential role of Chk1 in S phase progression through regulation of RNR2 expression.2008

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

      Biocbem. Biopbys. Res. Commun. 374

      Pages: 79-83

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Checkpoints meet transcription at a novel histone milestone (H3-T11).2008

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

      Cell Cycle 7

      Pages: 1555-1559

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Susceptibility of p27 kip1 knockout mice to urinary bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine may not simply be due to enhanced proliferatio.2008

    • Author(s)
      Hikosaka, A.
    • Journal Title

      Int. J. Cancer 122

      Pages: 1222-1228

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cdc2p controls the forkhead transcription factor Fkh2 by phosphorylation during sexual differentiation in fission yeast.2008

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

      EMBOJ. 27

      Pages: 132-142

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] DNA損傷部位への適切なdNTP供給機構2009

    • Author(s)
      中西真
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-10-02
    • Related Report
      2009 Annual Research Report
  • [Presentation] DNA損傷応答における新たなヒストン修飾H3-T11のリン酸化を介した転写制御2008

    • Author(s)
      中西真
    • Organizer
      第31回分子生物学会年会、第81回日本生化学学会大会合同大会シンポジウム
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2008-12-09
    • Related Report
      2008 Annual Research Report
  • [Presentation] 細胞周期と発がん2008

    • Author(s)
      中西真
    • Organizer
      第67回日本癌学会学術総会シンポジウム
    • Place of Presentation
      名古屋市センチュリーホール
    • Year and Date
      2008-10-28
    • Related Report
      2008 Annual Research Report
  • [Book] Checkpoint Controls and Targets in Cancer Therapy(Chapter6)2008

    • Author(s)
      Nakanishi, M.
    • Publisher
      Human Press.
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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