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Molecular mechanism of translational regulation mediated by the crosstalk between mTOR and Mnk signaling pathways in tumorigenesis

Research Project

Project/Area Number 15K07953
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionOsaka University of Pharmaceutical Sciences

Principal Investigator

Fukunaga Rikiro  大阪薬科大学, 薬学部, 教授(移行) (40189965)

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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsシグナル伝達 / プロテインキナーゼ / 細胞増殖 / 翻訳制御 / MAPキナーゼ / CRISPR/Cas9 / 翻訳調節
Outline of Final Research Achievements

To investigate translational regulation in tumor cell growth, we generated HeLa cells lacking the Mnk1 and/or Mnk2 genes by using the CRISPR/Cas9 method. We found that inhibition of mTORC1 resulted in upregulation of eIF4E phosphorylation and that this signal crosstalk was mediated by Mnk2 but not by Mnk1. We also found that stimulation of cells by growth factors resulted in upregulation of Mnk1-mediated phosphorylation of eIF4E but in suppression of Mnk2-mediated eIF4E phosphorylation, suggesting that Mnk2 is regulated, at least in part, by an unidentified mechanism that would be different from the MAPK pathway but linked to the PI3K-mTOR pathway. This study would raise the potential for combination treatments of mTOR and Mnk inhibitors for tumor therapies.

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 Int'l Joint Research (4 results) Presentation (3 results)

  • [Int'l Joint Research] Northwestern University(米国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Northwestern University(米国)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] Northwestern University(米国)

    • Related Report
      2015 Research-status Report
  • [Int'l Joint Research] Beatson Institute for Cancer Research(英国)

    • Related Report
      2015 Research-status Report
  • [Presentation] CRISPR/Cas9システムによるMnk1/Mnk2ノックアウトHeLa細胞の作成とシグナル伝達経路の解析2017

    • Author(s)
      小笠原慎,井上潤子,大谷侑平,金谷祥吾,水野和史,藤井忍,藤井俊裕,尾崎惠一,福永理己郎
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 増殖刺激によるMnkの活性化動態,およびmTOR/Mnk阻害剤の効果の解析2016

    • Author(s)
      金谷祥吾、辻野裕介、大谷侑平、藤井忍、井上晴嗣、福永理己郎
    • Organizer
      日本薬学会 近畿支部大会
    • Place of Presentation
      大阪薬科大学(大阪府高槻市)
    • Related Report
      2016 Research-status Report
  • [Presentation] CRISPR/Cas9システムによるMnk1遺伝子ノックアウトHeLa細胞の作成と解析2016

    • Author(s)
      井上潤子、大谷侑平、藤井忍、井上晴嗣、福永理己郎
    • Organizer
      日本薬学会 近畿支部大会
    • Place of Presentation
      大阪薬科大学(大阪府高槻市)
    • Related Report
      2016 Research-status Report

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Published: 2015-04-16   Modified: 2022-06-06  

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