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MgcRacGAPによる細胞周期と増殖分化の統合的調節機構の解析

Research Project

Project/Area Number 20058006
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe University of Tokyo

Principal Investigator

北村 俊雄  The University of Tokyo, 医科学研究所, 教授 (20282527)

Co-Investigator(Kenkyū-buntansha) 川島 敏行  東京大学, 医科学研究所, 助教 (10306839)
Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 2009: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2008: ¥3,000,000 (Direct Cost: ¥3,000,000)
Keywords細胞分裂 / 低分子量G蛋白質 / STAT / サイトキネシス / 転写因子
Research Abstract

細胞が分裂する際、娘細胞の一方に中央体(Midbody)が移行し中央体遺残物(Midbody remnant)となる。中央体遺残物にはMgcRacGAP、AuroraB、NFkBなど細胞増殖や分化に重要な働きをする分子が数多く含まれており、その意味において細胞は常に不均等分裂するといえる。我々は細胞分裂後に中央体遺残物を含む細胞と含まない細胞でその運命に差があるのではないかと考え、MgcRacGAP-GFP融合蛋白質を利用して分裂後の細胞を追跡した。その結果、分裂後に中央体(MgcRacGAP)を含む細胞が若干早く次の細胞周期に入る傾向が認められたが、統計的に有意な差ではなかった。
この実験を通じてMgcRacGAP-GFPが細胞分裂後に急速に消失する細胞が多いことが判明した。MgcRacGAPは細胞分裂期にはRho-GAPとして細胞質分裂の終了に重要な働きをする一方、間期にはRac-GAPとしてSTAT転写因子の活性化、核内移行に必須の働きをする興味深い蛋白質である(Minoshima et al. Dev Cell, 2003 ; Kawashima et al. J Cell Biol, 2006 ; Kawashima et al. Mol Cell Biol, 2009)。今回の実験の結果はMgcRacGAPがリン酸化による調節以外に、ユビキチン、スモ化などの調節により分解調節を受けている可能性を示唆した。

Report

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

    (42 results)

All 2010 2009 2008

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (28 results) Book (3 results)

  • [Journal Article] Hes1 immortalizes committed progenitors and plays a role in blast crisis transition in chronic myelogeneou leukemia.2010

    • Author(s)
      Nakahara, F
    • Journal Title

      Blood (in press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] AID-induced T-lymphoma or B-leukemia/lymphoma in a mouse BMT model.2010

    • Author(s)
      Komeno, Y
    • Journal Title

      Leukemia (in press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular bases of myelodysplastic syndromes : Lessons from animal models2009

    • Author(s)
      Komeno, Y
    • Journal Title

      J Cell.Physiol. 219

      Pages: 529-534

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Rac GTPase activating protein MgcRacGAP is an NLS-containing nuclear chaperone in the activation of STAT transcription factors2009

    • Author(s)
      Kawashima, T
    • Journal Title

      Mol Cell Biol. 29

      Pages: 1796-1813

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activating and inhibitory signals from an inhibitory receptor LMIR3/CLM-1 : LMIR3 augments LPS response through association with FcRg in mast cells2009

    • Author(s)
      Izawa, K
    • Journal Title

      J.Immunol. 183

      Pages: 925-936

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Rac GTPase activating protein MgcRacGAP is constitutively phosphorylated on serine 387 in the v-Src-transformed NIH3T3 cells2009

    • Author(s)
      Doki, N
    • Journal Title

      Cancer Science 100

      Pages: 1675-1679

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mixed-lineage-leukemia(MLL)fusion protein collaborates with Ras to induce a cute leukemia through aberrant Hox expression and Raf activation2009

    • Author(s)
      Ono, R
    • Journal Title

      Leukemia 23

      Pages: 2197-209

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of mouse LMIR5/CLM7 as an activating receptor: differential regulati on of LMIR5/CLM7 between mouse and human2008

    • Author(s)
      Yamanishi Y
    • Journal Title

      Blood 111

      Pages: 688-698

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] AML1 mutations induced MDS and MDS/AML in a mouse BMT model2008

    • Author(s)
      Watanabe-Okochi N
    • Journal Title

      Blood 111

      Pages: 4297-4308

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rac and Nuclear Translocation of STAT Transcription Factors2008

    • Author(s)
      Kawashima T
    • Journal Title

      Methods in Enzymology 439

      Pages: 171-189

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Rac GTPase activating protein MgcRacGAP is an NLS-containing nuclear chaperone in the activation of STAT transcription factors2008

    • Author(s)
      Kawashima T
    • Journal Title

      Molecular and Cellular Biology 29

      Pages: 1796-1813

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Learning from mouse BMT models for MDS and MPD2009

    • Author(s)
      Kitamura, T
    • Organizer
      MDS/MPN Meeting
    • Place of Presentation
      USA, ヒューストン
    • Related Report
      2009 Annual Research Report
  • [Presentation] Wnt modulators, SFRP-1 and SFRP-2 differentially regulate hematopoietic stem cells2009

    • Author(s)
      中島秀明
    • Organizer
      第71回日本血液学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2009 Annual Research Report
  • [Presentation] Constitutive phosphorylation of a RacGAP is involved in v-Src-induced transformation of NIH3T3 cells2009

    • Author(s)
      土岐典子
    • Organizer
      第71回日本血液学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2009 Annual Research Report
  • [Presentation] Analysis of C/EBPA mutations in AML, MDS by a mouse BMT model2009

    • Author(s)
      加藤菜穂子
    • Organizer
      第71回日本血液学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2009 Annual Research Report
  • [Presentation] Hes1 confers self-renewal capability on committed progenitors and induces CML BC-like disease2009

    • Author(s)
      中原史雄
    • Organizer
      第71回日本血液学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2009 Annual Research Report
  • [Presentation] Hes1による骨髄前駆細胞への自己複製能付与と、慢性骨髄性白血病における急性転化の誘導2009

    • Author(s)
      中原史雄
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] MgcRacGAPの恒常的リン酸化はv-SrcによるNIH3T3細胞の transform に関与する2009

    • Author(s)
      土岐典子
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] LMIR5のリガンドとしてTIM1およびTIM4を同定した2009

    • Author(s)
      山西吉典
    • Organizer
      第39回日本免疫学会総会・学術集会
    • Place of Presentation
      大阪
    • Related Report
      2009 Annual Research Report
  • [Presentation] LMIR3ノックアウトマウスの解析;LMIR3欠損はマウス腹膜炎モデルにおける致死率を改善する2009

    • Author(s)
      伊沢久未
    • Organizer
      第39回日本免疫学会総会・学術集会
    • Place of Presentation
      大阪
    • Related Report
      2009 Annual Research Report
  • [Presentation] ヒトLMIR/CD300ファミリー分子の解析:CD300CはFcRgammaと会合して活性化シグナルを伝達する2009

    • Author(s)
      高橋まり子
    • Organizer
      第39回日本免疫学会総会・学術集会
    • Place of Presentation
      大阪
    • Related Report
      2009 Annual Research Report
  • [Presentation] LMIR8/CLM-6はpDCマーカーである2009

    • Author(s)
      貝谷綾子
    • Organizer
      第39回日本免疫学会総会・学術集会
    • Place of Presentation
      大阪
    • Related Report
      2009 Annual Research Report
  • [Presentation] 活性化レセプターLMIR7とLMIR4の比較解析:FcRγとの会合から得られた知見2009

    • Author(s)
      榎本豊
    • Organizer
      第39回日本免疫学会総会・学術集会
    • Place of Presentation
      大阪
    • Related Report
      2009 Annual Research Report
  • [Presentation] An activating and inhibitory signal from an inhibitory receptor LMIR3/CLM-1 : LMIR3 augments LPS response through association with FcRγ in mast cells2009

    • Author(s)
      前原明絵
    • Organizer
      第39回日本免疫学会総会・学術集会
    • Place of Presentation
      大阪
    • Related Report
      2009 Annual Research Report
  • [Presentation] インターロイキン6(IL-6)阻害剤のスクリーニング法の開発と阻害剤の評価2008

    • Author(s)
      土屋秋穂
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-09
    • Related Report
      2008 Annual Research Report
  • [Presentation] Analysis of Mouse LMIR5/CLM-7 as An Activating Receptor : Differential Regulation of LMIR5/CLM-7 in Mouse Versus Human Cells2008

    • Author(s)
      Yamanishi Y
    • Organizer
      50th American Society of Hematology (ASH) Annual Meeting and Exposition
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2008-12-05
    • Related Report
      2008 Annual Research Report
  • [Presentation] 可溶性LMIR5はLPSによる炎症反応を増強する2008

    • Author(s)
      山西吉典
    • Organizer
      第38回日本免疫学会総会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-01
    • Related Report
      2008 Annual Research Report
  • [Presentation] 活性化レセプターLMIR7の機能解析2008

    • Author(s)
      榎本豊
    • Organizer
      第38回日本免疫学会総会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-01
    • Related Report
      2008 Annual Research Report
  • [Presentation] LMIR3はマスト細胞において細胞内領域のITIMを介した抑制化シグナルとIT削を有するFcRgammaとの会合を介した活性化シグナルを伝達する2008

    • Author(s)
      伊沢久未
    • Organizer
      第38回日本免疫学会総会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-01
    • Related Report
      2008 Annual Research Report
  • [Presentation] 活性化レセプターのLMIR6は末梢血の樹状細胞に高発現する2008

    • Author(s)
      杉内正弘
    • Organizer
      第38回日本免疫学会総会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-01
    • Related Report
      2008 Annual Research Report
  • [Presentation] BMTモデルを用いたAID高発現による白血病・リンパ腫の解析2008

    • Author(s)
      米野由希子
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-10-28
    • Related Report
      2008 Annual Research Report
  • [Presentation] 白血病、骨髄増殖性疾患、骨髄異形成症候群発症の分子メカニズム2008

    • Author(s)
      北村俊雄
    • Organizer
      第70回日本血液学会総会
    • Place of Presentation
      京都
    • Year and Date
      2008-10-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] AML,MDSでみられたC/EBPα変異体のマウスBMT model2008

    • Author(s)
      加藤菜穂子
    • Organizer
      第70回日本血液学会総会
    • Place of Presentation
      京都
    • Year and Date
      2008-10-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] BMTモデルを用いたAID高発現による白血病・リンパ腫の解析2008

    • Author(s)
      米野由希子
    • Organizer
      第70回日本血液学会総会
    • Place of Presentation
      京都
    • Year and Date
      2008-10-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] 新しいメカニズムでJAK/STATシグナルを抑制する阻害剤の同定2008

    • Author(s)
      川島敏行
    • Organizer
      第70回日本血液学会総会
    • Place of Presentation
      京都
    • Year and Date
      2008-10-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] Robo4の造血幹細胞における生理学的機能2008

    • Author(s)
      中島秀明
    • Organizer
      第70回日本血液学会総会
    • Place of Presentation
      京都
    • Year and Date
      2008-10-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] Analysis of mouse LMIR5/CLM-7 as an activating receptor : differential regulation of LMIR5/CLM-7 in mouse versus human cells2008

    • Author(s)
      Yamanishi Y
    • Organizer
      The 15^<th> East Asia Joint Conference
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2008-07-20
    • Related Report
      2008 Annual Research Report
  • [Presentation] 活性型レセプターLMIR5の機能解析 : マウスおよびヒトLMIR5の相違2008

    • Author(s)
      山西吉典
    • Organizer
      第4回麒麟塾
    • Place of Presentation
      品川
    • Year and Date
      2008-07-19
    • Related Report
      2008 Annual Research Report
  • [Presentation] Overexpression of AID causes both T and B lymphoma in a mouse BMT model2008

    • Author(s)
      Komeno Y
    • Organizer
      ISEH 37th Annual Scientific Meeting
    • Place of Presentation
      Boston, USA
    • Year and Date
      2008-07-09
    • Related Report
      2008 Annual Research Report
  • [Book] 細胞工学2009

    • Author(s)
      沖俊彦
    • Publisher
      株式会社学研メディカル秀潤社
    • Related Report
      2009 Annual Research Report
  • [Book] 臨床血液2009

    • Author(s)
      北村俊雄
    • Publisher
      社団法人 日本血液学会
    • Related Report
      2009 Annual Research Report
  • [Book] 日本臨床2009

    • Author(s)
      加藤菜穂子
    • Publisher
      株式会社 日本臨牀社
    • Related Report
      2009 Annual Research Report

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Published: 2008-04-01   Modified: 2018-03-28  

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