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Molecular mechanisms of growth control via TOR complex in response to inputs.

Research Project

Project/Area Number 17K07330
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Functional biochemistry
Research InstitutionNiigata University

Principal Investigator

Fukuda Tomoyuki  新潟大学, 医歯学系, 准教授 (90415282)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsTOR / TORC1 / シグナル伝達 / 細胞増殖 / 分裂酵母 / 栄養飢餓 / 遺伝学 / 細胞・組織 / 癌
Outline of Final Research Achievements

Target of rapamycin complex 1 (TORC1) is an evolutionarily conserved protein kinase complex that controls cell growth and metabolism. To understand the molecular mechanism of TORC1-mediated cell growth control, factors involved in TORC1 signaling have been screened for, identified and characterized using fission yeast as a model. This study has revealed that TORC1 is negatively regulated by three signaling pathways in response to nutrient availability. Moreover, a transcription factor, which regulates genes involved in protein synthesis, has been found to be stabilized by TORC1, suggesting that TORC1 promotes cell growth through the activation of protein synthesis via this transcription factor. Thus, this study provides insights into understanding of the mechanisms by which cells grow in response to nutrients.

Academic Significance and Societal Importance of the Research Achievements

本研究は分裂酵母をモデルに、TOR複合体の活性調節に関わる複数の経路と、TOR複合体の下流で増殖を促進する因子とを同定し、それぞれの特徴付けを行った。これらの経路や因子は高度に保存されているため、哺乳類の細胞増殖においてもTOR複合体が同様に制御されていると予想される。TOR複合体経路は多種の癌細胞で過度に活性化しており、癌の進行を促進することが知られている。また、TOR複合体は代謝や老化にも関与する。したがって、本研究で明らかになったTOR複合体の活性制御機構や下流の因子を標的に、抗腫瘍、アンチエイジング、糖尿病、肥満に関連する創薬や治療法の開発につながる可能性がある。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (11 results)

All 2019 2018 2017

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (6 results) (of which Invited: 1 results)

  • [Journal Article] The Rag GTPase-Ragulator complex attenuates TOR complex 1 signaling in fission yeast.2018

    • Author(s)
      Fukuda, T. and Shiozaki, K.
    • Journal Title

      Autophagy

      Volume: 印刷中 Pages: 1105-1106

    • DOI

      10.1080/15548627.2018.1444313

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Molecular mechanism and physiological functions of mitophagy in yeast2018

    • Author(s)
      Fukuda Tomoyuki、Kanki Tomotake
    • Journal Title

      PLANT MORPHOLOGY

      Volume: 30 Issue: 1 Pages: 31-36

    • DOI

      10.5685/plmorphol.30.31

    • NAID

      130007622409

    • ISSN
      0918-9726, 1884-4154
    • Related Report
      2018 Research-status Report
  • [Journal Article] TORC1シグナル伝達経路を介した細胞の栄養応答機構2018

    • Author(s)
      福田智行
    • Journal Title

      新潟医学会雑誌

      Volume: 132 Pages: 77-82

    • NAID

      120006763610

    • Related Report
      2018 Research-status Report
  • [Journal Article] Mechanisms and Physiological Roles of Mitophagy in Yeast2018

    • Author(s)
      Fukuda T, Kanki T
    • Journal Title

      Mol. Cells

      Volume: 41 Pages: 35-44

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ragulator and GATOR1 complexes promote fission yeast growth by attenuating TOR complex 1 through Rag GTPases2017

    • Author(s)
      Chia Kim Hou、Fukuda Tomoyuki、Sofyantoro Fajar、Matsuda Takato、Amai Takamitsu、Shiozaki Kazuhiro
    • Journal Title

      eLife

      Volume: 6

    • DOI

      10.7554/elife.30880

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 分裂酵母のTSC、GATOR1、Gcn2経路は、それぞれ独立にTORC1の窒素源応答を制御する2019

    • Author(s)
      福田智行
    • Organizer
      第9回TOR研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 分裂酵母のTOR複合体1を制御する複数の経路2019

    • Author(s)
      福田智行、神吉智丈、塩﨑一裕
    • Organizer
      酵母遺伝学フォーラム第52回研究報告会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 分裂酵母Rag二量体は富栄養条件下でもTOR複合体1を抑制して増殖を促す2018

    • Author(s)
      福田智行、神吉智丈、塩﨑一裕
    • Organizer
      酵母遺伝学フォーラム第51回研究報告会
    • Related Report
      2018 Research-status Report
  • [Presentation] 分裂酵母の TORC1 を負に制御する複数の経路2018

    • Author(s)
      福田智行
    • Organizer
      第8回TOR研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 分裂酵母のRag GTPase二量体はTOR複合体1を抑制することで増殖を促進する2017

    • Author(s)
      福田智行、塩﨑一裕
    • Organizer
      第58回新潟生化学懇話会
    • Related Report
      2017 Research-status Report
  • [Presentation] TORC1シグナル経路を介した細胞の栄養応答機構2017

    • Author(s)
      福田智行
    • Organizer
      第728回新潟医学会
    • Related Report
      2017 Research-status Report
    • Invited

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Published: 2017-04-28   Modified: 2021-02-19  

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