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Regulation of the ERK-MAPK cascade and cell-transformation by MEKsumoylation

Research Project

Project/Area Number 23890077
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Pathological medical chemistry
Research InstitutionThe University of Tokyo (2012)
Nagoya University (2011)

Principal Investigator

KUBOTA Yuji  東京大学, 医科学研究所, 助教 (70614973)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords癌 / ERK / SUMO / MAPK / Ras-MAPK症候群 / MEK
Research Abstract

We found MEK sumoylation strongly attenuated its kinase activity and inhibited the ERK pathway by disrupting the specific docking interaction between MEK and ERK. Interestingly, the Ras oncogene inhibited MEK sumoylation, and forced enhancement of MEK sumoylation suppressed Ras-induced cell transformation. These data indicates that the ablation of MEKsumoylation by the specific oncogene contributes to carcinogenesis.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • Research Products

    (15 results)

All 2013 2012 2011 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (12 results) Book (1 results)

  • [Journal Article] ユビキチンおよびユビキチン様タンパク質によるMAPキナーゼ経路の制御2012

    • Author(s)
      久保田裕二
    • Journal Title

      実験医学(増刊)

      Volume: 30 Pages: 72-79

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oncogenic Ras abrogates MEK SUMOylation that suppresses the ERK pathway and cell transformation2011

    • Author(s)
      Yuji Kubota, Pauline O'Grady, Haruo Saito, and Mutsuhiro Takekawa
    • Journal Title

      Nature Cell Biology

      Volume: 13 Pages: 282-291

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Presentation] 癌および先天性Ras/MAPK症候群における変異型MEKの異常活性化メカニズムの解明2013

    • Author(s)
      久保田裕二,武川睦寛
    • Organizer
      平成24年度文部科学省新学術領域研究「がん研究分野の特性等を踏まえた支援活動」冬期シンポジウム
    • Place of Presentation
      学術総合センター(東京都)
    • Year and Date
      2013-01-30
    • Related Report
      2012 Final Research Report
  • [Presentation] Molecular basis of constitutively active MEK mutants in the congenital Ras/MAPK syndromes and sporadic cancers2012

    • Author(s)
      久保田裕二、武川睦寛
    • Organizer
      第35回 日本分子生物学会年会
    • Place of Presentation
      マリンメッセ福岡(福岡県)
    • Year and Date
      2012-12-14
    • Related Report
      2012 Final Research Report
  • [Presentation] 癌及び先天性Ras/MAPK症候群におけるMEK変異体の異常活性化機構の解明2012

    • Author(s)
      久保田裕二,武川睦寛
    • Organizer
      「新学術領域研究」修飾シグナル病若手ワークショップ
    • Place of Presentation
      ホテルあかね(神奈川県)
    • Year and Date
      2012-10-03
    • Related Report
      2012 Final Research Report
  • [Presentation] 癌遺伝子Rasの新たな発癌機構-蛋白質SUMO化による細胞増殖ERKシグナル制御と癌におけるその破綻2012

    • Author(s)
      久保田裕二,武川睦寛
    • Organizer
      第49回日本臨床分子医学会学術集会
    • Place of Presentation
      みやこめっせ(京都府)
    • Year and Date
      2012-04-13
    • Related Report
      2012 Final Research Report
  • [Presentation] Negative regulation of the ERK pathway and cell transformation by MEK SUMOylation2011

    • Author(s)
      久保田裕二、武川睦寛
    • Organizer
      平成23年度がん若手研究者ワークショプ
    • Place of Presentation
      アートランドホテル蓼科(長野県)
    • Year and Date
      2011-08-31
    • Related Report
      2012 Final Research Report
  • [Presentation] Negative regulation of the ERK pathway and cell transformation by MEK SUMOylation2011

    • Author(s)
      久保田裕二
    • Organizer
      平成23年度がん若手研究者ワークショップ
    • Place of Presentation
      アートランドホテル蓼科(長野県)(口演発表)
    • Year and Date
      2011-08-31
    • Related Report
      2011 Annual Research Report
  • [Presentation] A novel activation mechanism of MEK1/2 mutants in the congenital Ras/MAPK syndromes and sporadic cancers2011

    • Author(s)
      久保田裕二,武川睦寛
    • Organizer
      第34回日本分子生物学会年
    • Place of Presentation
      横浜パシフィコ(神奈川県)
    • Related Report
      2012 Final Research Report
  • [Presentation] A novel activation mechanism of MEK1/2 mutants in the congenital Ras/MAPK syndromes and sporadic cancers2011

    • Author(s)
      久保田裕二
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜パシフィコ(神奈川県)(一般演題)(ポスター発表)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 癌遺伝子Rasの新たな発癌機構 -蛋白質SUMO化による細胞増殖ERKシグナル制御と癌におけるその破綻-(口演発表)

    • Author(s)
      久保田 裕二
    • Organizer
      第49回 日本臨床分子医学会学術集会
    • Place of Presentation
      みやこめっせ(京都府)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 癌及び先天性Ras/MAPK症候群におけるMEK変異体の異常活性化機構の解明と特異的阻害剤の同定 (口演発表)

    • Author(s)
      久保田 裕二
    • Organizer
      「新学術領域研究」修飾シグナル病 若手ワークショップ
    • Place of Presentation
      ホテルあかね(神奈川県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Molecular basis of constitutively active MEK mutants in the congenital Ras/MAPK syndromes and sporadic cancers. (ポスター発表、演題番号:4ST5-023)

    • Author(s)
      久保田 裕二
    • Organizer
      第35回 日本分子生物学会年会
    • Place of Presentation
      マリンメッセ福岡(福岡県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 癌および先天性Ras/MAPK症候群における変異型MEKの異常活性化メカニズムの解明と選択的阻害剤の開発

    • Author(s)
      久保田 裕二
    • Organizer
      平成24年度 文部科学省新学術領域研究「がん研究分野の特性等を踏まえた支援活動」冬期シンポジウム
    • Place of Presentation
      学術総合センター(東京都)
    • Related Report
      2012 Annual Research Report
  • [Book] ユビキチンおよびユビキチン様タンパク質によるMAPキナーゼ経路の制御2012

    • Author(s)
      久保田裕二、中亮介、武川睦寛
    • Publisher
      羊土社
    • Related Report
      2012 Final Research Report

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Published: 2011-09-05   Modified: 2019-07-29  

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