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Regulatory mechanism for the function of myocardin family members and its relation to cell phenotype

Research Project

Project/Area Number 20590279
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

HAYASHI Ken'ichiro  Osaka University, 医学系研究科, 准教授 (90238105)

Co-Investigator(Kenkyū-buntansha) SOBUE Kenji  大阪大学, 医学系研究科, 教授 (20112047)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2008: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsmyocardin / MRTF-A / B / importin α / β1 / G-actin / 核移行 / 平滑筋細胞形質転換 / MRTF-A/B / importin α/β1 / basic domain / myocardin family members / importinα / importin / 核移行シグナル
Research Abstract

Myocardin (Mycd), which is essential for the differentiation of the smooth-muscle cell lineage, is constitutively located in the nucleus, although its family members, myocardin-related transcription factors A and B (MRTF-A/B), mostly reside in the cytoplasm and translocate to the nucleus in response to Rho-signaling. The mechanism for their nuclear import is unclear. Here, we investigated the mechanism for the nuclear import of Mycd family members, and demonstrated any correlation between such mechanism and the phenotype of vascular smooth muscle cells (VSMCs). In cultured VSMCs, the knockdown of importin β1 inhibited the nuclear import of Mycd and MRTF-A/B. Their NH2-terminal basic domain (NB) was identified as a binding site for importin α/β1 by in vitro analyses. However, Mycd had a higher affinity for importin α/β1 than MRTF-A/B did, even in the absence of G-actin, and Mycd's affinity for importin α1/β1 was stronger than for any other importin α/β1 heterodimers. The binding of Mycd to importin α/β1 was insensitive to G-actin, whereas that of MRTF-A/B was differently inhibited by G-actin. In dedifferentiated VSMCs, the levels of importins α1 and β1 were reduced concomitant with down-regulation of Mycd, serum response factor, and SMC markers. By contrast, in differentiated VSMCs, their expressions were up-regulated. Thus, the nuclear import of Mycd family members in VSMCs depends on importin α/β1, and their relative affinities for importin α/β1 heterodimers determine the Mycds' nuclear import. The expression of the Mycds' nuclear import machineries is related to the expression levels of VSMC phenotype-dependent SMC markers.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (14 results)

All 2010 2009 2008

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (4 results)

  • [Journal Article] Nuclear import mechanism for myocardin family members and their correlation with vascular smooth muscle cell phenotype.2010

    • Author(s)
      Nakamura S, Hayashi K, Iwasaki K, Fujioka T, Egusa H, Yatani H, Sobue K.
    • Journal Title

      J Biol Chem 285

      Pages: 37314-37323

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Myocardin functions as an effective inducer of growth arrest and differentiation in human uterine leiomyosarcoma cells.2010

    • Author(s)
      Kimura Y., Morita T., Hayashi K., Miki T., Sobue K.
    • Journal Title

      Cancer Res 70

      Pages: 501-511

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Expression profiles of nestin in vascular smooth muscle cells in vivo and in vitro.2010

    • Author(s)
      Oikawa H., Hayashi K., Maesawa C., Masuda T., Sobue K.
    • Journal Title

      Exp Cell Res 316

      Pages: 940-950

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Nuclear import mechanism for myocardin family members and their correlation with vascular smooth muscle cell phenotype2010

    • Author(s)
      Nakamura S, Hayashi K, Iwasaki K, Fujioka T, Egusa H, Yatani H, Sobue K.
    • Journal Title

      J.Biol.Chem.

      Volume: 285 Pages: 37314-37323

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Myocardin functions as an effective inducer of growth arrest and differentiation in human uterine leiomyosarcoma cells2010

    • Author(s)
      Kimura Y., Morita T., Hayashi K., Miki T., Sobue K.
    • Journal Title

      Cancer Res. 70

      Pages: 501-511

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression profiles of nestin in vascular smooth muscle cells in vivo and in vitro2010

    • Author(s)
      Oikawa H., Hayashi K., Maesawa C., Masuda T., Sobue K. (equal contribution)
    • Journal Title

      Exp.Cell Res. 316

      Pages: 940-950

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glucocorticoid receptor-mediated expression of caldesmon regulates cell migration via the reorganization of the actin cytoskeleton.2008

    • Author(s)
      Mayanagi, T., Morita, T., Hayashi, K., Fukumoto, K., Sobue, K.
    • Journal Title

      J Biol Chem 283

      Pages: 31183-31196

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rho/ROCK signal regulates myogenic differentiation via MRTF-A/Smad-dependent transcription of the Id3 gene.2008

    • Author(s)
      Iwasaki, K., Hayashi, K., Fujioka,T., Sobue, K.
    • Journal Title

      J Biol Chem 283

      Pages: 21230-21241

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rho/ROCK signal regulates myogenic differentiation via MRTF-A/Smad-dependent transcription of the Id3 gene.2008

    • Author(s)
      Iwasaki, K., Hayashi, K., Fujioka, T., Sobue, K.
    • Journal Title

      J. Biol. Chem. 283

      Pages: 21230-21241

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glucocorticoid receptor-mediated expression of caldesmonregulates cell migration via the reorganization of the act in cytoskeleton.2008

    • Author(s)
      Mayanagi, T., Morita, T., Hayashi, K., Fukumoto, K., Sobue, K.
    • Journal Title

      J. Biol. Chem. 283

      Pages: 31183-31196

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] マイオカルディンはヒト平滑筋肉腫細胞において細胞増殖抑制と分化誘導に効果的な因子として働く2010

    • Author(s)
      木村泰典、森田強、林謙一郎、三木恒治、祖父江憲治
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-22
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] myocardinファミリーの核内移行メカニズム2010

    • Author(s)
      中村誠志、林謙一郎、岩崎一洋、江草宏、矢谷博文、祖父江憲治
    • Organizer
      第62回日本細胞生物学会
    • Place of Presentation
      大阪
    • Year and Date
      2010-06-21
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] Importin α1/β1により制御される転写調節因子myocardinの核内輸送におけるN末basic domainの役割2009

    • Author(s)
      中村誠志、林謙一郎、岩崎一洋、江草宏、矢谷博文、祖父江憲治
    • Organizer
      第61回日本細胞生物学会
    • Place of Presentation
      名古屋
    • Year and Date
      2009-06-02
    • Related Report
      2010 Final Research Report
  • [Presentation] Importin α1/β1により制御される転写調節因子 myocardin の核内輸送におけるN末 basic domain の役割2009

    • Author(s)
      中村誠志, 林謙一郎, 岩崎一洋, 江草宏, 矢谷博文, 祖父江憲治
    • Organizer
      第61回日本細胞生物学会
    • Place of Presentation
      名古屋
    • Year and Date
      2009-06-02
    • Related Report
      2009 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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