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プログラム細胞死を実行するプロテアーゼI CE/CED-3ファミリーの活性調節機構

Research Project

Project/Area Number 09780648
Research Category

Grant-in-Aid for Encouragement of Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Cell biology
Research InstitutionOsaka University

Principal Investigator

三浦 正幸  大阪大学, 医学部, 助教授 (50202338)

Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywordsカスパーゼ / ショウジョウバエ / 細胞死 / 線虫 / アポトーシス / プロテアーゼ / ICE / Bcl-2 / 酵母
Research Abstract

CED-4はcaspaseの活性化因子として細胞死の実行に深く関与している。CED-4の機能解析を生化学的・分子遺伝学的に行うことを目的としてショウジョウバエを用いたCED-4の機能評価系を確立した。ショウジョウバエ由来の培養細胞であるS2にCED-4を過剰に発現させることによってcaspaseの活性化を伴う細胞死を誘導することが出来た。CED-4によって活性化されるcaspaseをaffinitylabelによって同定した結果、dr ICEが活性化されていることが明らかになった。免疫沈降実験によって細胞内ではCED-4とdr ICEが複合体を形成することが明らかになり、caspaseとの直接の相互作用がその活性化に必要であることが示唆された。また、CED-4内のP-loop motifがcaspaseの活性化に重要であり、P-loopmutationはdominant negativeにCED-4による細胞死を抑制した。ショウジョウバエ複眼に過剰発現させたCED-4はcaspaseの活性化を伴った細胞死を誘導し、生体でのCED-4の機能を評価する系が確立された。

Report

(2 results)
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Araki,T.: "Caspase activity is required for nephrogenesis in the developiug mouse kulney" Expevimental Cell Research. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Suzuki,A.: "Caspase-3 inactivation to suppress Fas-inefiated apoptosis:identifiation of binding domain with P21 and ICP and inactivation machinery by p21." Oncogene. 18. 1239-1244 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Suzuki,A.: "Res stance to Fas-mefiated apoptosis:activation of caspase-3 is regulated by cell cycle regulator p21 WAF and IAP gene family ILP" Oncogene. 17. 931-939 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kanuka,H.: "Pro-apoptotic activity of C.elegans CED.4 in Droscphila:impl:cated Mechanisms for caspase activation." Pioc.Natl Acad.Sci U.S.A.96. 145-150 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hisahara,S.: "C elegans ant.-apoptotic gene ced-9 prevents ced-3-induced cell death in Drosophila cells." J.Cell Science. 111. 667-673 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Wang,S.: "Murine caspase-11,an ILE interacting protease,is essential for activation of ICE." Cell. 92. 501-509 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Miura,M.: "Apoptosis:its roles and mechanisms" Business Center for Academic Societies, 18 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sugimoto,A.: "Apoptosis Regulatory Genes" Kluwer Academic Publisher, in press (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Wang,S.ら: "Murine caspase-11, an ICE interacting protease, is essential for activation of ICE" Cell. 92. 501-509 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hisahara,S.ら: "C. elegans anti-apoptotic gene ced-9 prevents ced-3-induced cell death in Drosophila cells." J. Cell Sci.111. 667-673 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanaka,M.ら: "Insulin-like growth factor-I analog prevents apoptosis mediated through ICE-like protease of cojebellar external granuuar layer neurons : developmental stage-specific mechanisms of neuronal cell death" Neuroscience. (印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hisahara,S.ら: "ICE/CED-3 family execute olisodendrocytes apoptosis by tumor necrosis factor." J. Neurochem.69. 10-20 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shiraiwa,S.ら: "Bcl-2 prevents TNF- and FAS- induced cell death but not inhibit processing of caspase-3" Biomed. Res. 18. 405-411 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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