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Mechanisms underlying cell cycle regulation and induction of apoptosis by transcription factor p53.

Research Project

Project/Area Number 13470032
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionNippon Medical School

Principal Investigator

TANAKA Nobuyuki  Nippon Medical School, Department of Molecular Oncology, Institute of Gerontology, Professor, 大学院・医学研究科, 教授 (80222115)

Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥15,900,000 (Direct Cost: ¥15,900,000)
Fiscal Year 2003: ¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 2002: ¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 2001: ¥5,500,000 (Direct Cost: ¥5,500,000)
Keywordsp53 / apoptosis / Noxa / PUMA / Bcl-2 family proteins / BH3-only factors / mitochondria / gene knockout mice / 細胞周期 / Bcl-2ファミリー因子 / Bax / Bak / Bc1-2ファミリー因子
Research Abstract

Mechanisms underlying Cell cycle regulation and induction of apoptosis by transcription factor p53 have been extensively studied in the context of tumor suppression. During our studies, we identified a novel gene Noxa, whose induction is dependent on. Noxa encodes a BH3-only member of the Bcl-2 family proteins and, when ectopically expressed, it induces apoptosis. We studied the role of Noxa in vitro and in vivo, by the gene-targeting approach. The mouse embryonic fibroblasts deficient in Noxa (Noxa^<-/-> MEFs) showed notable resistance to oncogene-dependent apoptosis in response to DNA damage. These MEFs also showed increased sensitivity to oncogene-induced cell transformation in vitro. Furthermore, Noxa^<-/-> mice showed resistance to gastrointestinal death following X-ray irradiation, accompanied with impaired apoptosis in the epithelial cells of small intestinal crypts, thereby indicating the role of Noxa in the p53 response in vivo. After we published these results, gene knockout studies of Noxa related BH3-only member PUMA was published. In this experiment, decreased oncogene-dependent in MEFs, and also loss of Puma protected lymphocytes from apoptosis. Therefore, BH3-only factors are critical mediators of the apoptotic responses induced by p53.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Shibue, T. et al.: "Integral role of Noxa in p53-mediated apoptotic response."Genes Dev.. 17. 2233-2238 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hata, N. et al.: "Constitutive IFS-α/β signal for Efficient IFN-α/β gene induction by virus."Biochem.Biophys.Res.Commun.. 285. 518-525 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mitani, Y. et al.: "Cross talk of the interferon-α/β signalling complex with gp130 for effective interleukin-6 signalling."Genes Cells. 6. 631-640 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakaya, T. et al.: "Gene induction pathways mediated by distinct IRFs during viral infection."Biochem.Biophys.Res.Commun.. 283. 1150-1156 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sato, K. et al.: "Antiviral response by natural killer cells through TRAIL gene induction by IFN-α/β."Eur.J.Immunol.. 31. 3138-3146 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sato, M. et al.: "The interferon system and interferon regulatory factor transcription factors - studies from gene knockout mice."Cytokine Growth Factor Rev.. 12. 133-142 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Taniguchi, T. et al.: "IRF family of transcription factors as regulators of host defense."Annu.Rev.Immunol.. 19. 623-655 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shibue, T. et al.: "Integral role of Noxa in p53-mediated apoptotic response."Genes Dev.. 17. 2233-2238 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hata, N. et al.: "Constitutive IFN-a/b signal for efficient IFN-α/β gene induction by virus."Biochem.Biophys.Res.Commun.. 285. 518-525 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mitai, Y. et al.: "Cross talk of the interferon-α/β signalling complex with gp130 for effective interleukin-6 signalling."Genes Cells. 6. 631-640 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakaya, T. et al.: "Gene induction pathways mediated by distinct IRFs during viral infection."Biochem.Biophys.Res.Commun.. 283. 1150-1156 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sato, K. et al.: "Antiviral response by natural killer cells through TRAIL gene induction by IFN-α/β."Eur.J.Immunol.. 31. 3138-3146 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sato, M. et al.: "The interferon system and interferon regulatory factor transcription factors -studies from gene knockout mice."Cytokine Growth Factor Rev.. 12. 133-142 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Taniguchi, T. et al.: "IRF family of transcription factors as regulators of host defense."Annu.Rev.Immunol.. 19. 625-655 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shibue, T.et al.: "Integral role of Noxa in p53-mediated apoptotic response."Genes Dev.. 17. 2233-2238 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hata, N. et al.: "Constitutive IFN-α/β signal for efficient IFN-α/β gene induction by virus"Biochem. Biophys. Res. Commun.. 285. 518-525 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mitani, Y. et al.: "Cross talk of the interferon-α/β singnalling complex with gp130 for effective interleukin-6 signalling"Genes Cells. 6. 631-640 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakaya, T. et al.: "Gene induction pathways mediated by distinct IRFs during viral infection"Biochem. Biophys. Res. Commun.. 283. 1150-1156 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sato, K. et al.: "Antiviral response by natural killer cells through TRAIL gene induction by IFN-α/β"Eur. J. Immunol.. 31. 3138-3146 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sato, M. et al.: "The interferon system and interferon regulatory factor transcription factors - studies from gene knockout mice"Cytokine Growth Factor Rev.. 12. 133-142 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Taniguchi, T. et al.: "IRF family of transcription factors as regulators of host defense"Annu. Rev. Immunol.. 19. 623-655 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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