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2003 Fiscal Year Final Research Report Summary

Molecular mechanisms involved in non-apoptotic programmed cell death regulation

Research Project

Project/Area Number 14580708
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionNational Cancer Center Research Institute

Principal Investigator

KITANAKA Chifumi  National Cancer Center Research Institute, Biology Division, Section Head, 生物学部, 室長 (70260320)

Project Period (FY) 2002 – 2003
KeywordsRas / Apoptosis
Research Abstract

We used the in vitro model system for Ras-dependent non-apoptotic programmed cell death and dissected the molecular mechanism involved in the regulation of Ras-induced non-apoptotic programmed cell death. In general, caspase-independent, non-apoptotic programmed cell deaths are known to be mitochondria-dependent We therefore examined whether mitochondria is involved in Ras-induced non-apoptotic programmed cell death. We found no evidence of increased permeability of mitochondrial membrane during Ras-induced cell death, and Ras-induced cell death was inhibited neither by Bcl-xL nor by vMIA, which are known to be potent inhitibors of mitochondrial cell death. These results indicated that Ras-induced cell death belongs to a novel type of non-apoptotic programmed cell death that has never been reported. Dissection of the intracellular signaling pathway activated by Ras using Ras effector loop mutant revealed that the Pl3K pathway plays a critical role in the transduction of the death signal. Screening of pharmacological agents that inhibit or promote Ras-induced cell death identified Toxin B of Clostridium difficile as a potent inhibitor of Ras-induced cell death, suggesting that the Rho family of proteins may play an important role in the regulation of Ras-induced cell death. Use of dominant-negative mutants of the Rho family proteins revealed that Rac among others may have a key role in Ras-induced non-apoptotic programmed cell death.

  • Research Products

    (8 results)

All 2004 2003 Other

All Journal Article (8 results)

  • [Journal Article] Physical and functional interaction between BH3-only protein Hrk and Mitochondrial pore-forming protein p32.2004

    • Author(s)
      Sunayama J et al.
    • Journal Title

      Cell Death and Differentiation in press

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Non-apoptotic programmed cell death and cancer.2004

    • Author(s)
      Kitanaka C.
    • Journal Title

      Exp Med 22

      Pages: 1590-1597

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Physical and functional interaction between BH3-only protein Hrk and mitochondrial pore-forming protein p32.2004

    • Author(s)
      Sunayama J, et al.
    • Journal Title

      Cell Death Differ 11

      Pages: 771-781

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Forced expression of antisense 14-3-3beta RNA suppresses tumor growth in vitro and in vivo.2003

    • Author(s)
      Sugiyama A et al.
    • Journal Title

      Carcinogensis 24

      Pages: 1549-1559

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Guanine nucleotide exchange factor, Tiam1, directly binds to c-Myc and interferes with c-Myc-mediated apoptosis in Rat-1 fibroblasts.2003

    • Author(s)
      Otsuki Y et al.
    • Journal Title

      Journal of Biological Chemistry 278

      Pages: 5132-5140

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Forced expression of antisense 14-3-3beta RNA suppresses tumor growth in vitro and in vivo.2003

    • Author(s)
      Sugiyama A, et al.
    • Journal Title

      Carcinogenesis 24

      Pages: 1549-1559

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Guanine nucleotide exchange factor, Tiam1, directly binds to c-Myc and interferes withc-Myc-mediated apoptosis in Rat-1 fibroblasts.2003

    • Author(s)
      Otsuki Y, et al.
    • Journal Title

      J Biol Chem 278

      Pages: 5132-5140

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Non-apoptotic programmed cell deaths : existence and significance of programmed cell deaths having morphology and mechanism distinct from apoptosis.

    • Author(s)
      Kitanaka C.
    • Journal Title

      Yamagata Med J (in press)

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2006-07-11  

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