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The role of Anaphase-Promoting Co mplex(APC)Activator Cdh1 on cell motility

Research Project

Project/Area Number 20590315
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionKeio University

Principal Investigator

KUNINAKA Shinji  Keio University, 医学部, 助教 (10404336)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsCdh1 / APC / Rho / p190 / APC/C / C / stress fiber / 接着班 / 癌 / 浸潤転移 / Cdhl / TGC / TSC
Research Abstract

Cdh1 is an activator of the anaphase-promoting complex/cyclosome and contributes to mitotic exit and G1 maintenance by targeting cell-cycle proteins for degradation. Here, we found a novel function for Cdh1 as a regulator of Rho. The GTP-bound active Rho protein was apparently decreased in the Cdh1-depleted cells. Cdh1 formed a physical complex with the p190 protein, a major GAP for Rho, and stimulated the efficient ubiquitination of p190, both in in vitro and in vivo. The motility of Cdh1-depleted cells was impaired ; however, co-depletion of p190 rescued the migration activity of these cells. Moreover, homozygous Cdh1 gene-trapped mouse embryos exhibited similar phenotypes to those observed for Rho-associated kinase I and II knockout mice, suggesting the in vivo significance of Cdh1/p190/Rho axis.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (19 results)

All 2011 2010 2009 2008 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (10 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Establishment of a choriocarcinoma model from immortalized normal extravillous trophoblast cells transduced with HRASV12.2011

    • Author(s)
      Kobayashi Y, Shimizu T, Naoe H, Ueki A, Ishizawa J, Chiyoda T, Onishi N, Sugihara E, Nagano O, Banno K, Kuninaka S, Aoki D, Saya H
    • Journal Title

      Am J Pathol (in press)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] The cell cycle regulator Cdh1 controls the pool sizes of hematopoietic stem cells and mature lineage progenitors by protecting from genotoxic stress.2011

    • Author(s)
      Ishizawa J, Kuninaka S, Sugihara E, Naoe H, Kobayashi Y, Chiyoda T, Ueki A, Araki K, Yamamura KI, Matsuzaki Y, Nakajima H, Ikeda Y, Okamoto S, Saya H
    • Journal Title

      Cancer Sci. 102

      Pages: 1349-7006

    • NAID

      10029293305

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] c-MYC overexpression with loss of Ink4a/Arf transforms bone marrow stromal cells into osteosarcoma accompanied by loss of adipogenesis.2010

    • Author(s)
      Shimizu T, Ishikawa T, Sugihara E, Kuninaka S, Miyamoto T, Mabuchi Y, Matsuzaki Y, Tsunoda T, Miya F, Morioka H, Nakayama R, Kobayashi E, Toyama Y, Kawai A, Ichikawa H, Hasegawa T, Okada S, Ito T, Ikeda Y, Suda T, Saya H
    • Journal Title

      Oncogene 29

      Pages: 5687-99

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] The anaphase-promoting complex/cyclosome activator Cdh1 modulates Rho GTPase by targeting p190 RhoGAP for degradation.2010

    • Author(s)
      Naoe H, Araki K, Nagano O, Kobayashi Y, Ishizawa J, Chiyoda T, Shimizu T, Yamamura K, Sasaki Y, Saya H, Kuninaka S
    • Journal Title

      Mol Cell Biol 30

      Pages: 3994-4005

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] c-MYC overexpression with loss of Ink4a/Arf transforms bone marrow stromal cells into osteosarcoma accompanied by loss of adipogenesis.2010

    • Author(s)
      Shimizu, Kuninaka, S, et al.
    • Journal Title

      Oncogene

      Volume: 29 Pages: 5687-99

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The APC/C activator Cdh1 modulates Rho GTPase by targeting p190 RhoGAP for degradation.2010

    • Author(s)
      Naoe, Kuninaka, S, et al.
    • Journal Title

      Mol Cell Biol

      Volume: 30 Pages: 3994-4005

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] APC/C活性化因子Cdh1/Fzr1のRho制御因子としての新しい役割2010

    • Author(s)
      國仲慎治、他
    • Organizer
      第69回日本癌学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-24
    • Related Report
      2010 Final Research Report
  • [Presentation] APC/C活性化因子Cdh1/Fzr1のRho制御因子としての新しい役割2010

    • Author(s)
      國仲慎治, 他
    • Organizer
      第68回日本癌学会総会
    • Place of Presentation
      大阪、大阪国際会議場
    • Year and Date
      2010-09-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] The APC/C activator Cdh1 modulates Rho GTPase by targeting p190 RhoGAP for degradation.2010

    • Author(s)
      Naoe, Kuninaka S, et al.
    • Organizer
      EMBO Workshop : The Interface between the Ubiquitin Family and the DNA Damage Response
    • Place of Presentation
      Red Island, Rovinj, Croatia
    • Year and Date
      2010-09-02
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] APC/C activator Cdh1 coordinately regulates cell cycle and differentiation in tronhoblast stem cells2009

    • Author(s)
      國仲慎治, 他
    • Organizer
      第68回日本癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] Anaphase promoting complex (APC) activator Cdh1 modulates RhoGTPase activity by targeting p190 RhoGAP for degradation2009

    • Author(s)
      直江秀昭、國仲慎治、他
    • Organizer
      第68回日本癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-02
    • Related Report
      2010 Final Research Report
  • [Presentation] APC/C activator Cdh1 coordinately regulates cell cycle and differentiation in trophoblast stem cells2009

    • Author(s)
      國仲慎治、他
    • Organizer
      第68回日本癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-02
    • Related Report
      2010 Final Research Report
  • [Presentation] Anaphase promoting complex(APC)activator Cdh1 modulates RhoGTPase activity by targeting p190 RhoGAP for degradation2009

    • Author(s)
      直江秀昭, 國仲慎治, 他
    • Organizer
      第68回日本癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-02
    • Related Report
      2009 Annual Research Report
  • [Presentation] 胎盤から見た細胞周期因子APC/cdh1の機能2008

    • Author(s)
      佐谷秀行、國仲慎治、他
    • 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
      2008-12-11
    • Related Report
      2010 Final Research Report
  • [Presentation] 胎盤から見た細胞周期因子APC/cdhlの機能2008

    • Author(s)
      佐谷秀行, 國仲慎治, 他
    • 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
      2008-12-11
    • Related Report
      2008 Annual Research Report
  • [Presentation] Anaphase promoting complex(APC)活性化因子cdh1はRhoGTPaseの新規調節因子である2008

    • Author(s)
      直江秀昭、國仲慎治、他
    • Organizer
      第67回日本癌学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-10-28
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Book] 細胞周期フロンティア(佐方功幸・稲垣昌樹・岸本健雄編)2010

    • Author(s)
      國仲慎治,佐谷秀行
    • Publisher
      共立出版
    • Related Report
      2010 Final Research Report
  • [Book] 細胞周期フロンティア(佐方功幸・稲垣昌樹・岸本健雄編)2010

    • Author(s)
      國仲慎治, 佐谷秀行
    • Total Pages
      252
    • Publisher
      共立出版
    • Related Report
      2010 Annual Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report

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

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