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Involvement of ubiquitin system on the hepatitis B virus X protein (HBx)-mediated transactivation activity

Research Project

Project/Area Number 17590274
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

TOKUNAGA Fuminori  Osaka City University, Graduate School of Medicine, Associated Professor, 大学院医学研究科, 助教授 (00212069)

Co-Investigator(Kenkyū-buntansha) IWAI Kazuhiro  Osaka City University, Graduate School of Medicine, Professor, 大学院医学研究科, 教授 (60252459)
KIRISAKO Takayoshi  Osaka City University, Graduate School of Medicine, Assistant, 大学院医学研究科, 助手 (30347497)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsprotein / enzyme / virus / transcription / 蛋白質
Research Abstract

We have identified an RING-IBR-RING (RBR) family ubiquitin ligase, HOIL-1L, as a predominant intracellular isoform of HOIL-1 (heme-oxidized IRP2 ligase-1). HOIL-1L forms a high molecular mass (〜600 kDa) complex with HOIP (HOIL-1L-interacting protein) in vivo. HOIP also belongs to RBR family, and the HOIL-1L/HOIP complex exhibits ubiquitin polymerization activity in vitro. To examine the physiological function of HOIL-1L/HOIP, we first screened the effect of HOIL-1L/HOIP on transcriptional activity, since HOIL-1 has shown to bind protein kinase C and hepatitis B virus X protein, and both of them affect transcription. Then, we found by luciferase reporter assay that combined expression of HOIL-1L and HOIP, but not by single expression of respective ligase, specifically induced NF-KB activation. Indeed, co-expression of HOIL-1L/HOIP caused intranuclear translocation of p65 and p50, and enhanced phosphorylation of IKBa. Using various domain-deleted mutants, we identified that the RING domains of HOIP played a crucial role on the NF-KB activation. Notably, a dysfunctional RING-finger mutant of HOIP inhibited TNF-a-and TAK1-mediated NF-KB activation, but had no effect on NIK-mediated NF-KB activation. These results indicate that HOIL-1L/HOIP activates canonical NF-KB pathway through the ubiquitin ligase activity of HOIP. The ligase complex may have a pivotal role on the inflammation, anti-apoptosis, and immune system through the regulation of NF-KB pathway.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (12 results)

All 2006 2005

All Journal Article (11 results) Book (1 results)

  • [Journal Article] Characterization of endoplasmic reticulum-associated degradation of a protein S mutant identified in a family of quantitative protein S deficiency2006

    • Author(s)
      Tsuda, H. et al.
    • Journal Title

      Thromb. Res. 117・3

      Pages: 323-331

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] A ubiquitin ligase complex assembles linear polyubiquitin chain2006

    • Author(s)
      Kirisako, T. et al.
    • Journal Title

      EMBOJ. 25・20

      Pages: 4877-4887

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Mutual regulation of conventional protein kinase C and a ubiquitin ligase complex2006

    • Author(s)
      Nakamura, M. et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 351・2

      Pages: 340-347

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Characterization of endoplasmic reticulum-associated degradation of a protein S mutant identified in a family of quantitative protein S deficiency2006

    • Author(s)
      Tsuda, H. et al.
    • Journal Title

      Thromb. Res. 117

      Pages: 323-331

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A ubiquitin ligase complex assembles linear polyubiquitin chain2006

    • Author(s)
      Kirisako, T. et al.
    • Journal Title

      EMBO J. 25

      Pages: 4877-4887

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Mutual regulation of conventional protein kinase C and a ubiquitin ligase complex2006

    • Author(s)
      Nakamura, M. et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 351

      Pages: 340-2347

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A ubiquitin ligase complex assembles linear polyubiquitin chain2006

    • Author(s)
      Kirisako, T. et al.
    • Journal Title

      EMBO J. 25・20

      Pages: 4877-4887

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Characterization of endoplasmic reticulum-associated degradation of a protein S mutant identified in a family of quantitative protein S deficiency2006

    • Author(s)
      Tsuda H., et al.
    • Journal Title

      Thromb.Res. 117

      Pages: 323-331

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Involvement of heme regulatory motif in heme-mediated ubiquitination and degradation of IRP22005

    • Author(s)
      Ishikawa, H. et al.
    • Journal Title

      Mol. Cell 19・2

      Pages: 171-181

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Involvement of heme regulatory motif in heme-mediated ubiquitination and degradation of IRP22005

    • Author(s)
      Ishikawa, H. et al.
    • Journal Title

      Mol. Cell 19

      Pages: 171-181

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Involvement of heme regulatory motif in heme-mediated ubiquitination and degradation of IRP22005

    • Author(s)
      Ishikawa H., et al.
    • Journal Title

      Mol.Cell 19

      Pages: 171-181

    • Related Report
      2005 Annual Research Report
  • [Book] 実験医学増刊 細胞内タンパク質の社会学2005

    • Author(s)
      徳永 文稔
    • Total Pages
      208
    • Publisher
      羊土社
    • Related Report
      2005 Annual Research Report

URL: 

Published: 2005-04-01   Modified: 2016-04-21  

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