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The molecular mechanism regulating ubiquitination of aberrant plasma membrane protein

Research Project

Project/Area Number 25893275
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionKwansei Gakuin University

Principal Investigator

OKIYONEDA Tsukasa  関西学院大学, 理工学部, 准教授 (90398248)

Project Period (FY) 2013-08-30 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords脱ユビキチン化 / CFTR / タンパク質品質管理 / ユビキチン
Outline of Final Research Achievements

Here, we sought to identify the deubiquitination enzyme (DUB) involved in the peripheral protein quality control mechanism that eliminates aberrant plasma membrane proteins such as ΔF508 CFTR. Analysis of a panel of DUB inhibitors discovered that inhibition of proteasome-associated DUB increased the cell surface expression and stability of ΔF508 CFTR. Moreover, endocytosis of ΔF508 CFTR was dramatically inhibited by inhibitors of proteasome-associated DUB. These results provide a novel regulatory mechanism that the proteasome-associated deubiquitination stimulates the elimination of aberrant plasma membrane proteins from the cell surface.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • Research Products

    (9 results)

All 2014 2013 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (4 results) (of which Invited: 4 results) Remarks (2 results)

  • [Journal Article] Peripheral quality control mechanism eliminating aberrant proteins from the plasma membrane2014

    • Author(s)
      Okiyoneda T
    • Journal Title

      Seikagaku

      Volume: Feb;86(1) Pages: 54-8

    • NAID

      40020011065

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanism-based corrector combination restores ΔF508-CFTR folding and function.2013

    • Author(s)
      Okiyoneda T, Veit G, Dekkers JF, Bagdany M, Soya N, Xu H, Roldan A, Verkman AS, Kurth M, Simon A, Hegedus T, Beekman JM, Lukacs GL
    • Journal Title

      Nat Chem Biol

      Volume: Jul;9(7) Issue: 7 Pages: 444-54

    • DOI

      10.1038/nchembio.1253

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ubiquitination-dependent quality control of hERG K+ channel with acquired and inherited conformational defect at the plasma membrane.2013

    • Author(s)
      Apaja PM, Foo B, Okiyoneda T, Valinsky WC, Barriere H, Atanasiu R, Ficker E, Lukacs GL, Shrier A.
    • Journal Title

      Mol Biol Cell

      Volume: Dec;24(24) Issue: 24 Pages: 3787-804

    • DOI

      10.1091/mbc.e13-07-0417

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] ユビキチン化による膜タンパク質CFTRの品質管理機構2014

    • Author(s)
      沖米田 司
    • Organizer
      日本生化学会大会
    • Place of Presentation
      国立京都国際会館(京都市)
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] CFTR quality control checkpoints as drug target2014

    • Author(s)
      Tsukasa Okiyoneda
    • Organizer
      Cystic Fibrosis in Asia from baslcs to clinics
    • Place of Presentation
      名古屋大学(名古屋市)
    • Year and Date
      2014-09-29 – 2014-09-30
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Post-ERにおける膜タンパク質CFTR のプロテオスタシス

    • Author(s)
      沖米田 司
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートピアホテル(神戸)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 嚢胞性線維症の薬物療法を目指した CFTR コレクターの分類と相乗効果

    • Author(s)
      沖米田 司
    • Organizer
      日本薬学会第134回年会
    • Place of Presentation
      熊本大学(熊本)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Remarks] 沖米田研究室 web ページ

    • URL

      http://sci-tech.ksc.kwansei.ac.jp/~okiyoneda/okilab.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 関西学院大学 理工学部 沖米田研究室

    • URL

      http://sci-tech.ksc.kwansei.ac.jp/~okiyoneda/okilab.html

    • Related Report
      2013 Annual Research Report

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Published: 2013-09-12   Modified: 2019-07-29  

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