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Post-translational regulation of Hes1 in nerual stem cells

Research Project

Project/Area Number 26440122
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Developmental biology
Research InstitutionKyoto University

Principal Investigator

Kobayashi Taeko  京都大学, ウイルス・再生医科学研究所, 助教 (40402804)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsHes1 / オシレーション / 翻訳後修飾 / 幹細胞分化 / 発現振動 / リプレッサー活性 / タンパク質分解 / 神経幹細胞
Outline of Final Research Achievements

Hes1 regulates the maintenance and the differentiation of stem cells by its dynamic expression. Previous studies demonstrated that Hes1 expression oscillates in stem cells, and that the oscillation contributes to their potency and differentiation fates. However, the molecular mechanisms regulating the oscillatory expression of Hes1 protein have not been fully identified.
We have focused on the post-translational regulation of Hes1 protein and tried to identify regulatory factors from the binding partners of Hes1 protein. We identified Usp27x and its homologs as new deubiquitinases (DUBs) of Hes1. We reported that these DUBs stabilize and modulate Hes1 protein dynamics by removing ubiquitin molecules, and thereby regulate neuronal differentiation of stem cells (Kobayashi et al, 2015). Moreover, we identified some amino acid residues crucial for Hes1 functions by post-translational regulation. We also identified new factors bound to recombinant Hes1.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (12 results)

All 2015 2014 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) Remarks (3 results)

  • [Journal Article] Deubiquitinating enzymes regulate Hes1 stability and neuronal differentiation.2015

    • Author(s)
      Taeko Kobayashi, Yumiko Iwamoto, Kazuhiro Takashima, Akihiro Isomura, Yoichi Kosodo, Koichi Kawakami, Tomoki Nishioka, Kozo Kaibuchi, Ryoichiro Kageyama
    • Journal Title

      FEBS Journal

      Volume: 印刷中 Issue: 13 Pages: 2475-2487

    • DOI

      10.1111/febs.13290

    • NAID

      120005670897

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression dynamics and functions of Hes factors in development and diseases.2014

    • Author(s)
      Kobayashi T, Kageyama R.
    • Journal Title

      Curr Top Dev Biol.

      Volume: 110 Pages: 263-283

    • DOI

      10.1016/b978-0-12-405943-6.00007-5

    • ISBN
      9780124059436
    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel and robust transplantation reveals the acquisition of polarized processes by cortical cells derived from mouse and human pluripotent stem cells2014

    • Author(s)
      Fumiaki Nagashima, Ikuo K Suzuki, Atsunori Shitamukai, Haruko Sakaguchi, Misato Iwashita, Taeko Kobayashi, Shigenobu Tone, Kazunori Toida, Pierre Vanderhaeghen, Yoichi Kosodo
    • Journal Title

      Stem cells and development

      Volume: (in press) Issue: 18 Pages: 2129-2142

    • DOI

      10.1089/scd.2013.0251

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] The roles and mechanism of ultradian oscillatory expression of the mouse Hes genes.2014

    • Author(s)
      Harima Y, Imayoshi I, Shimojo H, Kobayashi T, Kageyama R.
    • Journal Title

      Semin Cell Dev Biol.

      Volume: 34 Pages: 85-90

    • DOI

      10.1016/j.semcdb.2014.04.038

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] リソソーム活性の上昇は神経幹細胞の休眠状態を維持するのに必須である2015

    • Author(s)
      小林 妙子、岩本由美子、影山 龍一郎
    • Organizer
      BMB2015(第38回日本分子生物学会年会、第88回日本生化学会大会 合同大会)
    • Place of Presentation
      神戸、ポートアイランド
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] Deubiquitinating Enzymes Regulate Hes1 Stability and Neuronal Differentiation2015

    • Author(s)
      小林妙子
    • Organizer
      The CDB Symposium 2015 "Time in Development"
    • Place of Presentation
      神戸 理研CDB
    • Year and Date
      2015-03-23 – 2015-03-25
    • Related Report
      2014 Research-status Report
  • [Presentation] Hes1の脱ユビキチン化酵素はHes1タンパク質の安定性と機能を制御する2014

    • Author(s)
      小林妙子
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都 国立京都国際会館
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Research-status Report
  • [Presentation] 発現振動する転写因子Hes1の解析2014

    • Author(s)
      小林妙子
    • Organizer
      シンポジウム「分子から生命へ」
    • Place of Presentation
      京都大学 益川ホール
    • Year and Date
      2014-07-26
    • Related Report
      2014 Research-status Report
  • [Presentation] Deubiquitination modulates Hes1 repressor activity by Hes1 protein stabilization2014

    • Author(s)
      小林妙子
    • Organizer
      5th International Congress on Stem Cells and Tissue Formation
    • Place of Presentation
      Dresden, Germany
    • Year and Date
      2014-07-08 – 2014-07-11
    • Related Report
      2014 Research-status Report
  • [Remarks] 京都大学ウイルス研究所 増殖制御学分野 影山研究室

    • URL

      http://www.virus.kyoto-u.ac.jp/Lab/Kageyama/publication_all.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 京都大学ウイルス研究所 増殖制御学分野

    • URL

      http://www.virus.kyoto-u.ac.jp/Lab/Kageyama/publication.html

    • Related Report
      2015 Research-status Report
  • [Remarks] 京都大学 ウイルス研究所 増殖制御学分野

    • URL

      http://www.virus.kyoto-u.ac.jp/Lab/Kageyama/index.html

    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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