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Functional analysis of a novel E3 ubiquitin ligase, c-MIR

Research Project

Project/Area Number 16590405
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionRIKEN

Principal Investigator

ISHICO Satoshi  RIKEN, Infectious Immunity Team, Team Leader, 感染免疫応答研究チーム, チームリーダー (10273781)

Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
Keywordsubiquitin / antigen presentation / ubiquitin ligase / MHC Class II / endocytosis / B7-2 / transgenic mouse / immunosuppressor / MHC class II / E3ユビキチンリガーゼ / 抗原提示 / in situ hybridization / real time PCR / 細胞分画
Research Abstract

We previously reported a novel E3 ubiquitin ligase (E3)^4, designated as c-MIR, which targets B7-2 to lysosomal degradation and down-regulates the B7-2 surface expression through ubiquitination of its cytoplasmic tail. B7-2 is well known as a co-stimulatory molecule for antigen presentation, suggesting that the manipulation of c-MIR expression modulates immune responses in vivo. To examine this hypothesis, we generated genetically modified mice in which c-MIR was expressed under an invariant chain (li) promoter. Dendritic cells (DCs) derived from genetically engineered mice showed low ability to present antigens. In addition, these mice showed resistance to the onset of experimental autoimmune encephalomyelitis (EAE) and an impaired development of CD4 T cells in the thymus and the periphery. These findings led us to conclude that MHC class II (MHC II) is an additional target for c-MIR. Indeed, forced expression of c-MIR in several B cell lines down-regulated the surface expression of MHC II, and downregulation was found to depend on the presence of a single lysine residue in the cytoplasmic tail of the I-A β chain. In a reconstitution system using 293T cells, we found that the lysine residue at position 225 in the I-A β chain was ubiquitinated by c-MIR. To our knowledge, c-MIR is the first example of an E3 that is capable of inhibiting MHC II expression. Our findings suggest that c-MIR might potently regulate immune responses in vivo.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (18 results)

All 2006 2005 2004

All Journal Article (16 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] A novel family of membrane-bound E3 ubiquitin ligases2006

    • Author(s)
      Ohmura-Hoshino, M., Goto, E., Matsuki, Y., Aoki, M., Mito, M., Uematsu, M., Hotta, H., Ishido, S.
    • Journal Title

      The Journal of Biochemistry (In press)

    • NAID

      10018842614

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Inhibition of MHC class II expression and immune responses by c-MIR12006

    • Author(s)
      Ohmura-Hoshino, M., Matsuki, Y., Aoki, M., Goto, E., Mito, M., M.Uematsu, Kakiuchi, T., Hotta, H., Ishido, S.
    • Journal Title

      The Journal of Immunology (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 膜結合型新規E3ユビキチンリガーゼファミリー2006

    • Author(s)
      星野真理, 後藤栄治, 石戸聡
    • Journal Title

      実験医学 (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Single-point mutations of hepatitis C virus NS3 that impair p53 interaction and anti-apoptotic activity of NS3.2006

    • Author(s)
      Tanaka M, Nagano-Fujii M, Deng L, Ishido S, Sada K, Hotta H.
    • Journal Title

      Biochemical and Biophysical Research Communications 340(3)

      Pages: 792-799

    • NAID

      120000943971

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] ユビキチンとウイルス感染2006

    • Author(s)
      石戸聡
    • Journal Title

      医学のあゆみ 別冊

      Pages: 108-113

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] A novel family of membrane-bound E3 ubiquitin ligases2006

    • Author(s)
      Ohmura-Hoshino M., Goto, E., Matsuki, Y., Aoki, M., Mito, M., Uematsu, M., Hotta, H., Ishido, S.
    • Journal Title

      The Journal of Biochemistry (in Press)

    • NAID

      10018842614

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Inhibition of MHC class II expression and immune responses by c-MIR12006

    • Author(s)
      Ohmura-Hoshino, M., Matsuki, Y., Aoki, M., Goto, E., Mito, M., M.Uematsu, Kakiuchi, T., Hotta H., Ishido S.
    • Journal Title

      The Journal of Immunology (in Press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Makuketugogata sinki E3 yubikitinrigahzefamily2006

    • Author(s)
      Ohmura-Hoshino M., Goto, E., Ishido, S.
    • Journal Title

      Jikken Igaku (in Press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Single-point mutations of hepatitis C virus NS3 that impair p53 interaction and anti-apoptotic activity of NS3.2006

    • Author(s)
      Tanaka M, Nagano-Fujii M, Deng L, Ishido S, Sada K, Hotta H.
    • Journal Title

      Biochemical and Biophysical Research Communicaitons 340(3)

      Pages: 792-799

    • NAID

      120000943971

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] yubikitin to uirusukansen2006

    • Author(s)
      Ishido, S.
    • Journal Title

      Igaku no Ayumi separate vol.

      Pages: 108-113

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] KSHV ni taisuru Mennekiouto2006

    • Author(s)
      Ishido, S.
    • Journal Title

      Nihon Rinsyo

      Pages: 568-575

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] KSHVに対する免疫応答2005

    • Author(s)
      石戸聡
    • Journal Title

      日本臨牀

      Pages: 568-575

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Links Hepatitis C virus NS5Aprotein interacts with 2',5'-oligoadenylate synthetase and inhibits antiviral activity of IFN in an IFN sensitivity-determining region-independent manner.2004

    • Author(s)
      Taguchi, T.
    • Journal Title

      Journal of General Virology 85(4)

      Pages: 959-969

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Links AIRE functions as an E3 ubiquitin ligase2004

    • Author(s)
      Uchida, D.
    • Journal Title

      Journal of Experimental Medicine 19,199(2)

      Pages: 167-172

    • Related Report
      2004 Annual Research Report
  • [Journal Article] ユビキチンとウイルス感染2004

    • Author(s)
      石戸 聡
    • Journal Title

      医学のあゆみ 211(1)

      Pages: 108-113

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 新たな免疫制御性E3ユビキチンリンガーゼファミリー2004

    • Author(s)
      石戸 聡
    • Journal Title

      Molecular Medicine 40

      Pages: 312-320

    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] ヘルペスウイルス免疫回避分子を機能評価できる細胞株2005

    • Inventor(s)
      石戸聡
    • Industrial Property Rights Holder
      独立行政法人理化学研究所
    • Filing Date
      2005-10-20
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] ヘルペスウィルス免疫回避分子を機能評価できる細胞株2005

    • Inventor(s)
      石戸聡
    • Industrial Property Rights Holder
      独立行政法人理化学研究所
    • Filing Date
      2005-10-20
    • Related Report
      2005 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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