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Degradation mechanism of dystrophin short isoform, Dp71

Research Project

Project/Area Number 15K09629
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Fujimoto Takahiro  京都府立医科大学, 医学(系)研究科(研究院), 講師 (10446114)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsジストロフィン / Dp71 / 蛋白分解 / プロテアソーム / リン酸化 / 会合蛋白 / 分子間相互作用 / 脳神経細胞 / 知的障害 / 分子機序 / モデル細胞
Outline of Final Research Achievements

We investigated the posttranslational regulatory mechanisms of Dp71 expression in PC12 cells and found that the constitutive expression levels of Dp71 in PC12 cells were sensitive to proteasomal inhibition. The ectopic expression of FLAG-tagged ubiquitin revealed that Dp71 was ubiquitinated intracellularly. Interestingly, proteasomal inhibition was accompanied by a posttranslational accumulation of modified Dp71, which was restored by lambda protein phosphatase treatment in vitro, indicating that phosphorylation is responsible for the modification and affects the proteasome-dependent degradation of Dp71. Furthermore, proteasomal activity-sensitive phosphorylated Dp71 is closely associated with syntrophin, and syntrophin is also regulated by proteasomal activity in a similar way to Dp71, suggesting that the posttranslational regulatory machinery for Dp71 level is coupled with Dp71-syntrophin molecular complex. Thus, the phosphorylation-UPS regulates Dp71-associated protein complex.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (7 results)

All 2017 2016 Other

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

  • [Journal Article] Dp71 is regulated by phosphorylation and ubiquitin-proteasome system in neuronal cells.2017

    • Author(s)
      Fujimoto T, Yaoi T, Fushiki S, Itoh K.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 492(3) Issue: 3 Pages: 349-355

    • DOI

      10.1016/j.bbrc.2017.08.108

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HEK293 cells express dystrophin Dp71 with nucleus-specific localization of Dp71ab.2016

    • Author(s)
      Nishida A, Yasuno S, Takeuchi A, Awano H, Lee T, Niba ET, Fujimoto T, Itoh K, Takeshima Y, Nishio H, Matsuo M.
    • Journal Title

      Histochem Cell Biol.

      Volume: 146 Issue: 3 Pages: 301-309

    • DOI

      10.1007/s00418-016-1439-2

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] 脳型ジストロフィンの分子病態解析に基づく知的障害治療法の探索2017

    • Author(s)
      藤本崇宏、伊東恭子
    • Organizer
      第120回 日本小児科学会学術集会
    • Place of Presentation
      東京・品川・グランドプリンスホテル新高輪
    • Year and Date
      2017-04-14
    • Related Report
      2016 Research-status Report
  • [Presentation] 脳型ジストロフィンの分子病態解析に基づく知的障害治療法の探索2017

    • Author(s)
      藤本 崇宏、伊東 恭子
    • Organizer
      第120回日本小児科学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ジストロフィン遺伝子産物であるDp71はリン酸化とユビキチンプロテアソーム系によって発現制御される2017

    • Author(s)
      藤本崇宏、矢追毅、伏木信次、伊東恭子
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Annual Research Report
  • [Remarks] 京都府立医科大学 医学研究科 分子病態病理学

    • URL

      http://www.f.kpu-m.ac.jp/k/neurpath/index.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 京都府立医科大学大学院医学研究科分子病態病理学ホームページ

    • URL

      http://www.f.kpu-m.ac.jp/k/neurpath/index.html

    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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