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Molecular analysis of anti-apoptotic action in MALT lymphoma and its clinical application for diagnosis and treatment.

Research Project

Project/Area Number 17591023
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionAichi Medical University School of Medicine (2006)
Aichi Cancer Center Research Institute (2005)

Principal Investigator

HOSOKAWA Yoshitaka  Aichi Medical University School of Medicine, Department of Biochemistry, Professor, 医学部, 教授 (60229193)

Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsMalignant lymphoma / apoptosis / Chromosome translocation / プロテオミクス
Research Abstract

API2-MALT1. t(11;18)(q21;q21) is a characteristic chromosomal translocation in mucosa-associated lymphoid tissue (MALT) type lymphoma, and this translocation results in chimeric transcript of API2 (Apoptosis Inhibitor 2, also known as c-IAP2)-MALT1 (Mucosa-Associated Lymphoma Translocation gene 1). To identify proteins that bind API2-MALT1 chimeric protein, we employed coimmunoprecipitation and SDS PAGE analysis, followed by liquid chromatography-electrospray ionization tandem mass spectrometry. As a result, Smac, Htra2, and TRAF2 were identified as API2-MALT1-binding proteins.
Immunoprecipitation analysis demonstrated that ectopically expressed API2-MALT1 protein indeed binds to these endogeneous proteins. Furthermore, API2-MALT1 protein significantly inhibited Smac-promoted apoptosis in UV irradiated HeLa cells. These data strongly suggest that API2-MALT1 can block apoptosis, at least in part, by inhibiting Smac-mediated apoptotic pathway. Further study is warranted to investigate the detailed molecular mechanism of API2-MALT1 and its clinical application.

Report

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

    (15 results)

All 2006 2005 Other

All Journal Article (15 results)

  • [Journal Article] Molecular pathogenesis of MALT lymphoma : two signaling pathways underlying the antiapoptotic effect of API2-MALT1 fusion protein.2006

    • Author(s)
      Nakagawa M et al.
    • Journal Title

      leukemia 20

      Pages: 929-936

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Molecular pathogenesis of MALT lymphoma : two signaling pathways underlying the antiapoptotic effect of API2-MALT1 fusion protein.2006

    • Author(s)
      Nakagawa M, Seto M, Hosokawa Y.
    • Journal Title

      Leukemia 20

      Pages: 929-936

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Molecular pathogenesis of MALT lymphoma : two signaling pathways underlying the antiapoptotic of API2-MALT1 fusion protein2006

    • Author(s)
      Nakagawa M et al.
    • Journal Title

      Leukemia 20

      Pages: 929-936

    • Related Report
      2006 Annual Research Report
  • [Journal Article] API2-MALT1 fusion protein induces transcriptional activation of the API2 gene through NF-κB binding elements; evidence for a positive feed-back loop pathway resulting in unremitting NF-κB activation.2005

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

      Biochem. Biophys. Res. Commun 334

      Pages: 51-60

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] MALT1 contains nuclear export signals and regulates cytoplasmic localization of BCL10.2005

    • Author(s)
      Nakagawa M et al.
    • Journal Title

      Blood 106

      Pages: 4210-4216

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Anti-apoptotic action of API2-MALT1 fusion protein involved in t(11;18)(q21;q21) MALT lymphoma.2005

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

      Apoptosis 10

      Pages: 25-34

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] MALTリンパ腫におけるNF-kBの活性化と抗アポトーシス作用2005

    • Author(s)
      中川雅人, 細川好孝
    • Journal Title

      血液・腫瘍科 51

      Pages: 433-440

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] API2-MALT1 fusion protein induces transcriptional activation of the API2 gene through NF-кB binding elements; evidence for a positive feed-back loop pathway resulting in unremitting NF-кB activation.2005

    • Author(s)
      Hosokawa Y, Suzuki H, Nakagawa M, Lee TH, Seto M.
    • Journal Title

      Biochem.Biophys.Res.Commun. 334

      Pages: 51-60

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] MALT1 contains nuclear export signals and regulates cytoplasmic localization of BCL10.2005

    • Author(s)
      Nakagawa M, Hosokawa Y, Yonezumi M, Izumiyama K, Suzuki R, Tsuzuki S, Asaka M, Seto M.
    • Journal Title

      Blood 106

      Pages: 4210-4216

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Anti-apoptotic action of API2-MALT1 fusion protein involved in t(11;18)(q21;q21) MALT lymphoma. Review Article2005

    • Author(s)
      Hosokawa Y.
    • Journal Title

      Apoptosis 10

      Pages: 25-34

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Anti-apoptotic action of API2-MALT1 fusion protein involved in t(11;18)(q21;q21) MALT lymphoma.2005

    • Author(s)
      Hosokawa et al.
    • Journal Title

      Apotosis 10

      Pages: 25-34

    • Related Report
      2005 Annual Research Report
  • [Journal Article] API2-MALT1 fusion protein induces transcriptional activation of the API2 gene through NF-κB binding elements ; evidence for a positive feed-back loop pathway resulting in unremitting NF-κB activation.2005

    • Author(s)
      Hosokawa et al.
    • Journal Title

      B.B.R.C. 334

      Pages: 51-60

    • Related Report
      2005 Annual Research Report
  • [Journal Article] MALT1 contains nuclear export signal and regulates cytoplasmic localization of BCL10.2005

    • Author(s)
      Nakagawa et al.
    • Journal Title

      Blood 106

      Pages: 4210-4216

    • Related Report
      2005 Annual Research Report
  • [Journal Article] MALTリンパ腫におけるNF-kBの活性化と抗アポトーシス作用2005

    • Author(s)
      中川雅夫, 細川好孝
    • Journal Title

      血液腫瘍科 51

      Pages: 433-439

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Molecular pathogenesis of MALT lymphoma : two signaling pathways underlying anti-apoptotic effect of API2-MALT1 fusion protein

    • Author(s)
      Nakagawa et al.
    • Journal Title

      Leukemia (In press)

    • Related Report
      2005 Annual Research Report

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

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