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A novel mechanism for inhibition of TGF-β family signaling by HTRA1

Research Project

Project/Area Number 21890079
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionNiigata University

Principal Investigator

NOZAKI Hiroaki  Niigata University, 医歯学総合病院, 助教 (20547567)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2010: ¥1,235,000 (Direct Cost: ¥950,000、Indirect Cost: ¥285,000)
Fiscal Year 2009: ¥1,365,000 (Direct Cost: ¥1,050,000、Indirect Cost: ¥315,000)
KeywordsCARASIL / TGF-β / BMP-2 / BMP-4 / small vessel disease / HTRA1 / TGF-βファミリー / TGF-β1
Research Abstract

HTRA1, a serine protease, decreases the signaling of TGF-β family members such as TGF-β and BMPs, but the mechanism remains unkown. TGF-β and BMPs are synthesized as a proprotein and cleaved into mature form by furin in the trans-Golgi network. This study elucidated that HTRA1 cleaves the proprotein in the endoplasmic reticulum, resulting in reduced mature form and decreased the signaling by interfering with furin-dependent cleavage of TGF-β family members.

Report

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

    (7 results)

All 2011 2010 2009 Other

All Journal Article (3 results) (of which Peer Reviewed: 1 results) Presentation (4 results)

  • [Journal Article] Cerebral small-vessel disease protein HTRAI controls the amount of TGF-{beta}1 via cleavage of proTGF-{beta}l.2011

    • Author(s)
      Shiga A, Nozaki H, Onodera O, et al.
    • Journal Title

      Hum Mol Genetics 20(9)

      Pages: 1800-1810

    • Related Report
      2010 Final Research Report
  • [Journal Article] High Temperature Requirement Protein A1 による Bone Morphogenetic Protein-2/4シグナル伝達の阻害機序2010

    • Author(s)
      野崎洋明
    • Journal Title

      新潟医学会雑誌 1(124)

      Pages: 16-28

    • NAID

      120006747842

    • Related Report
      2010 Final Research Report
  • [Journal Article] Cerebral small-vessel disease protein HTRA1 controls the amountof TGF-{beta}1 via cleavage of proTGF-{beta}1.

    • Author(s)
      Shiga A, Nozaki H, Onodera O, etal.
    • Journal Title

      Human Molecular Genetics

      Volume: (Epub ahead of print)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] HTRA1 controls BMP-2/4 signaling via cleavage of proBMP-2/4 : implication for molecular pathogenesis of hereditary cerebral small vessel disease2010

    • Author(s)
      Nozaki H
    • Organizer
      48^<th>Annual Meeting Neuroscience 2010
    • Place of Presentation
      San Diego, CA, US
    • Year and Date
      2010-11-14
    • Related Report
      2010 Annual Research Report
  • [Presentation] HTRA1 controls BMP-2/4 signaling via cleavage of proBMP-2/42010

    • Author(s)
      Nozaki H.
    • Organizer
      implication for molecular pathogenesis of hereditary cerebral small vessel disease.
    • Place of Presentation
      48^<th> Annual Meeting Neuroscience
    • Related Report
      2010 Final Research Report
  • [Presentation] The molecular mechanism of regulation of TGF-β1 signaling by HtrA1 : implication for pathogenesis of CARASIL (Hereditary cerebral small vessel disease).2009

    • Author(s)
      Megumi Nihonmatsu
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-12-09
    • Related Report
      2009 Annual Research Report
  • [Presentation] The molecular mechanism of regulation of TGF-β 1 signaling by HTRA1 implication for pathogenesis of CARASIL(Hereditary cerebral small vessel disease)

    • Author(s)
      Nihonmatsu M.
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      2009
    • Related Report
      2010 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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