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Functional analyses of Exip, a new splicing variant of p38 which binds to anti-inflammatory drug.

Research Project

Project/Area Number 15510188
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Living organism molecular science
Research InstitutionRIKEN

Principal Investigator

SUDO Tatsuhiko  RIKEN, Antibiotics Laboratory, Senior Research Scientist, 長田抗生物質研究室, 先任研究員 (30260227)

Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥3,000,000 (Direct Cost: ¥3,000,000)
Keywordsp38 / Exip / Tollip / IL-1 / IRAK / Innate immunity / Inflammatory / Splicing / ストレス / 薬剤開発 / 転写後修飾 / MAPキナーゼ
Research Abstract

Based on the plan, the experiments were conducted and the results mentioned below were obtained.
1.Analysis of an Exip binding protein
By using yeast two-hybrid screening, we found that Exip, but not p38α, binds to Tollip (Toll interacting protein) which is involved in Interleukin-1(IL-1) signaling pathway as a component of the receptor proximal complex and impaired NF-κB activity. Moreover, Exip binds to another component of the complex, IRAK (IL-1 associating kinase). Exogenous-expression of Exip resulted in down-regulation of NF-κB activities both in HeLa and HEK293T cells. Together, these results demonstrate that Exip can be a new component of NF-κB pathway, and contribute to a comprehensive understanding of the signal transduction pathway in the inflammatory responses
2.Regulation of Exip expression
By using newly raised antibody specific for Exip, we identified that the antibody specifically recognize Exip in HL-60 and THP-1 in addition to exogenously expressed Exip. Its expression was enhanced by heat treatment but not by inflammatory cytokines.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (18 results)

All 2004 2003 Other

All Journal Article (15 results) Publications (3 results)

  • [Journal Article] Exip, a splicing variant of p38α, participates in interleukin-1 receptor proximal complex and downregulates NF-_κB pathway2004

    • Author(s)
      Yagasaki Y., Sudo T., Osada H.
    • Journal Title

      FEBS Letters 575

      Pages: 136-140

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] p38α mitogen-activated protein kinase plays a critical role in cardiomyocyte survival but not in cardiac hypertrophic growth in response to pressure2004

    • Author(s)
      Nishida K.et al.17/24
    • Journal Title

      Molecular and Cellular Biology 24

      Pages: 10611-10620

    • 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
  • [Journal Article] Role of p38 mitogen-activated protein kinase in thrombus formation2004

    • Author(s)
      Sakurai K., Matsuo Y., Sudo T., Takuwa Y., Kimura, S., Kasuya Y.
    • Journal Title

      Journal of Receptors and Signal Transduction 24

      Pages: 283-296

    • 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
  • [Journal Article] Involvement of Apoptosis Signal-Regulating Kinase-1 on Angiotensin II-induced Monocyte Chemoattractant Protein-1 Expression2004

    • Author(s)
      Omura T, Sudo T et al.8/12
    • Journal Title

      Arterioscler Thromb Vasc Biol 24

      Pages: 270-275

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Endothelin-1-induced cardiac hypertrophy is inhibited by activation of peroxisome proliferator-activated receptor-α partly via blockade of c-JNK pathway2004

    • Author(s)
      Irukayama-Tomobe Y, Sudo T et al.8/10
    • Journal Title

      Circulation 109

      Pages: 904-910

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Involvement of apoptosis signal-regulating kinase-1 on angiotensin II-induced monocyte chemoattractant protein-1 expression.2004

    • Author(s)
      Omura T.
    • Journal Title

      Arterioscler Thromb.Vasc.Biol. 24

      Pages: 270-275

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Endothelin-1-induced cardiac hypertrophy is inhibited by activation of peroxisome proliferator-activated receptor-α partly via blockade of c-Jun NH2-terminal kinase pathway.2004

    • Author(s)
      Irukayama-Tomobe Y.
    • Journal Title

      Circulation 109

      Pages: 904-910

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Exip, a splicing variant of p38α, participates in interleukin-1 receptor proximal complex and down-regulates NF-κB pathway.2004

    • Author(s)
      Yagasaki, Y.
    • Journal Title

      FEBS Lett. 575

      Pages: 136-140

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Role of p38 mitogen-activated protein kinase in thrombus formation.2004

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

      J.Recept.Signal Transduc. 24

      Pages: 283-296

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] p38α mitogen-activated protein kinase plays a critical role in cardiomyocyte survival but not in cardiac hypertrophic growth in response to pressure overload.2004

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

      Mol.Cell Biol. 24

      Pages: 10611-10620

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Exip, a splicing variant of p38α, participates in interleukin-1 receptor proximal complex and downregulates NF-κB pathway2004

    • Author(s)
      Yagasaki Y., Sudo T., Osada H.
    • Journal Title

      FEBS Letters 575

      Pages: 136-140

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Involvement of Apoptosis Signal-Regulating Kinase-1 on Angiotensin II-induced Monocyte Chemoattractant Protein-1 Expression2004

    • Author(s)
      Omura T, Sudo T et al. 8/12
    • Journal Title

      Arterioscler Thromb Vasc Biol 24

      Pages: 270-275

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Endothelin-1-induced cardiac hypertrophy is inhibited by activation of peroxisome proliferator-activated receptor-α partly via blockade of c-JNK pathway2004

    • Author(s)
      Irukayama-Tomobe Y, Sudo T et al. 8/10
    • Journal Title

      Circulation 109

      Pages: 904-910

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Renal abnormalities in mice caused by insufficiency of p38α2003

    • Author(s)
      Maruyama M, Yagasaki Y, Sudo T, Osada H
    • Journal Title

      Journal of Receptors and Signal Transduction 23

      Pages: 173-183

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Renal abnormalities in mice caused by insufficiency of p38α.2003

    • Author(s)
      Maruyama, M.
    • Journal Title

      J.Recept.Signal Trnsduct. 23

      Pages: 173-183

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Maruyama M, Yagasaki Y, Sudo T, Osada H: "Renal abnormalities in mice caused by insufficiency of p38α"Journal of Receptors and Signal Transduction. 23. 173-183 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Omura T, Sudo T et al.. 8/12: "Involvement of Apoptosis Signal-Regulating Kinase-1 on Angiotensin II-induced Monocyte Chemoattractant Protein-1 Expression"Arterioscler Thromb Vasc Biol. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Irukayama-Tomobe Y, Sudo T et al.. 8/10: "Endothelin-1-induced cardiac hypertrophy is inhibited by activation of peroxisome proliferator-activated receptor-α partly via blockade of c-JNK pathway"Circulation. (in press). (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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