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Elucidation of the molecular mechanisms of carcinogenesis by the VHL, tumor suppressor gene

Research Project

Project/Area Number 13470041
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

ASO Teijiro  Kochi University, Faculty of Medicine, Professor, 医学部, 教授 (20291289)

Co-Investigator(Kenkyū-buntansha) KITAJIMA Shigetaka  Tokyo Medical and Dental University, Medical Research Institute, Professor, 難治疾患研究所, 教授 (30186241)
Project Period (FY) 2001 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥11,100,000 (Direct Cost: ¥11,100,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2003: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2002: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2001: ¥3,700,000 (Direct Cost: ¥3,700,000)
KeywordsElongin / Transcription elongation / VHL tumor suppressor gene / RNA polymerase II / Gene targeting / ES cell / ノックアウトマウス / アポトーシス / 細胞早期老化 / p53 / p38 MAPK / エロンガン / 散発性腎癌 / 分化 / von Hippel-Lindau病 / VHL癌抑制蛋白
Research Abstract

1.Generation and characterization of Elongin A-deficient ES cells
To investigate the function of Elongin A in vivo, the two alleles of the Elongin A gene have been disrupted by homologous recombination in murine embryonic stem(ES) cells. The Elongin A-deficient ES cells are viable, but possess markedly enlarged cell mass and show a slow growth phenotype because they undergo a delayed mitosis. The cDNA microarray and RNase protection assay using the wild-type and Elongin A-deficient ES cells indicate that the expression of only a small subset of genes is significantly affected in the mutant cells. These findings suggest that Elongin A regulates transcription of a subset but not all of genes, and reveal a linkage between Elongin A function and cell cycle progression.
2.Identification of a novel transcription elongation factor, Elongin A3
We have identified a novel transcription elongation factor, Elongin A3. Mechanistic studies have demonstrated that Elongin A3 stimulate the rate of transcription elongation by RNA polymerase II and is capable of forming a stable complex with Elongin BC. In contrast to Elongin A, however, its transcriptional activity is not activated by Elongin BC. Structure-function analysis using fusion proteins composed of Elongin A3 and Elongin A revealed that the COOH-terminal region of Elongin A is important for the activation by Elongin BC.
3.Identification of EloA-BP1, a novel Elongin A binding protein with an exonuclease homology domain
We have identified a novel protein, termed EloA-BP1, which interacts with the NH2-termini of both Elongin A and SII. EloA-BP1 is composed of 1221 amino acids and its mRNA is expressed ubiquitously. As EloA-BP1 possesses the exonuclease domain at its COOH-terminus, this protein may have role to maintain the fidelity of transcriptional products.

Report

(5 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (17 results)

All 2004 2003 2002 2001 Other

All Journal Article (9 results) Book (1 results) Publications (7 results)

  • [Journal Article] 「研究成果報告書概要(欧文)」より2004

    • Author(s)
      Tamura, K.
    • Journal Title

      J.Med.Technol.(Igaku Shoin) 48

      Pages: 223-231

    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mammalian Elongin A is not essential for cell viability but is required for proper cell-cycle progression with limited alteration of gene expression.2003

    • Author(s)
      Yamazaki, K.
    • Journal Title

      J.Biol.Chem. 278

      Pages: 13585-13589

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of EloA-BP1, a novel Elongin A binding protein with an exonuclease homology domain.2003

    • Author(s)
      Tamura, K
    • Journal Title

      Biochem.Biophys.Res.Commun. 309

      Pages: 189-195

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mammalian Elongin A is not essential for cell viability but is required for proper cell cycle progression with limited alteration of gene expression.2003

    • Author(s)
      Yamazaki, K.
    • Journal Title

      J.Biol.Chem. 278

      Pages: 13585-13589

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of EloA-BP1, a novel Elongin A binding protein with an exonuclease homology domain.2003

    • Author(s)
      Tamura, K.
    • Journal Title

      Biochem.Biophys.Res.Commun. 276

      Pages: 189-195

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification and biochemical characterization of a novel transcription elongation factor, Elongin A3.2002

    • Author(s)
      Yamazaki, K.
    • Journal Title

      J.Biol.Chem. 277

      Pages: 26444-26451

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Homocysteine induces programmed cell death in human vascular endothelial cells through activation of the unfolded protein response.2001

    • Author(s)
      Zhang, C.
    • Journal Title

      J.Biol.Chem. 276

      Pages: 35867-35874

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Activation of JNK and transcriptional repressor ATF3/LRF1 through the IRE1/TRAF2 pathway is Implicated in human vascular endothelial cell death by homocysteine.2001

    • Author(s)
      Zhang, C.
    • Journal Title

      Biochem.Biophys.Res.Commun. 289

      Pages: 718-724

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] c-Jun NH2-terminal kinase and transcriptional repressor ATF3/LRF-1 is activated through endoplasmic reticulum stress and implicated in human vascular endothelial cell death by homocysteine.2001

    • Author(s)
      Zhang, C.
    • Journal Title

      Biochem.Biophys.Res.Commun. 289

      Pages: 718-724

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 臨床検査2004

    • Author(s)
      田村 賢司
    • Total Pages
      9
    • Publisher
      医学書院
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Publications] Yamazaki, K.: "Mammalian Elongin A is not essential for cell viability but is required for proper cell cycle progression with limited alteration of gene expression."J.Blot.Chem.. 277. 13585-13589 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tamura, K: "Identification of EloA-BP1, a novel Elongin A binding protein with an exonuclease homology domain."Biochem.Biophys.Res.Comm.. 309. 189-195 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 田村 賢司: "臨床検査"医学書院. 9 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamazaki, K.: "Identification and biochemical characterization of a novel transcription elongation factor, Elongin A3"J. Biol. Chem.. 277. 26444-26451 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamazaki, K: "Mammalian Elongin A is not essential for cell viability but required for proper cell-cycle progression with limited alteration of gene expression"J. Biol. Chem. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Zhang, C.: "Homocysteine induces programmed cell death in human vascular endothelial cells throuth activation of the unfolded protein response"J.Biol.Chem.. 276. 35867-35874 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Zhang, C.: "Activation of JNK and transcriptional repressor ATF3/LRF1 through the IRE1/TRAF2 pathway is implicated in human vascular endothelial cell death by homocysteine"Biochem.Biophys.Res.Commun.. 289. 718-724 (2001)

    • Related Report
      2001 Annual Research Report

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

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