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Molecular mechanism of E2F regulation of cell proliferation and tumor suppression

Research Project

Project/Area Number 15K06957
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Molecular biology
Research InstitutionKwansei Gakuin University

Principal Investigator

Ohtani Kiyoshi  関西学院大学, 理工学部, 教授 (30201974)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsE2F / RB / ARF / p53 / がん化抑制 / 細胞増殖 / がん抑制遺伝子 / pRB / リン酸化 / 相互作用因子 / CDK
Outline of Final Research Achievements

We examined the molecular mechanism of how the transcription factor E2F, the principal target of the tumor suppressor RB, discriminates between growth-related genes and tumor suppressor genes. We examined the possibility of differential phosphorylation of E2F1, which plays major roles in tumor suppression, by generating mutants of 65 sites that could be phosphorylated. No mutants showed differential ability to activate tumor suppressor genes. We thought of the possibility that different cofactors contribute to activation of growth-related genes and tumor suppressor genes. We explored novel factors, which interacts with E2F1 by co-immunoprecipitation and yeast two-hybrid system. These screening gave 3 and 20 candidates, respectively. We analyzed these factors and found that DDX5, WDR1 and GTF2H2 enhance E2F1 activation of tumor suppressor genes.

Report

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

    (19 results)

All 2018 2017 2016 2015

All Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (14 results) (of which Int'l Joint Research: 1 results) Book (1 results)

  • [Journal Article] Ectopic expression of the CDK inhibitor p21Cip1 enhances deregulated E2F activity and increases cancer cell-specific cytotoxic gene expression mediated by the ARF tumor suppressor promoter2017

    • Author(s)
      Kenta Kurayoshi, Ayumi Shiromoto, Eiko Ozono, Ritsuko Iwanaga, Andrew P. Bradford, Keigo Araki, Kiyoshi Ohtani
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 483(1) Issue: 1 Pages: 107-114

    • DOI

      10.1016/j.bbrc.2016.12.185

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The phosphatidyl inositol 3 kinase pathway does not suppress activation of the ARF and BIM genes by deregulated E2F1 activity2017

    • Author(s)
      Kenta Kurayoshi, Junko Okuno, Eiko Ozono, Ritsuko Iwanaga, Andrew P. Bradford, Kazuyuki Kugawa, Keigo Araki, Kiyoshi Ohtani
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 482(4) Issue: 4 Pages: 784-790

    • DOI

      10.1016/j.bbrc.2016.11.111

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Interaction Mode of the Acidic Region of the Cell Cycle Transcription Factor DP1 with TFIIH2016

    • Author(s)
      Masahiko Okuda, Keigo Araki, Kiyoshi Ohtani, Yoshifumi Nishimura
    • Journal Title

      Journal of Molecular Biology

      Volume: 428(24) Issue: 24 Pages: 4993-5006

    • DOI

      10.1016/j.jmb.2016.11.001

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of novel target genes specifically activated by deregulated E2F in human normal fibroblasts2015

    • Author(s)
      Kitamura H, Ozono E, Iwanaga R, Bradford AP, Okuno J, Shimizu E, Kurayoshi K, Kugawa K, Toh H, Ohtani K.
    • Journal Title

      Genes Cells

      Volume: 20 Pages: 739-757

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] p27Cip1 induces apoptosis specifically in cancer cells through up-regulation of the E2F activity2017

    • Author(s)
      倉吉健太, 大谷清
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] がん抑制遺伝子発現制御における活性化型E2FのN末端領域の役割2017

    • Author(s)
      尾田衡弥, 荒木啓吾, 大谷清
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] サイクリン依存性キナーゼによる制御を外れたE2F1活性抑制機構の解析2017

    • Author(s)
      津田大輔, 荒木啓吾, 大谷清
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 転写因子E2F1のN末端領域に対する新規相互作用因子WDR1の機能解析2017

    • Author(s)
      根岸泰明, 荒木啓吾, 大谷清
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] アデノウイルスE1Aによる転写因子E2F3の新しい発現制御機構2017

    • Author(s)
      服部拓, 荒木啓吾, 大谷清
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 転写因子E2Fの新たなメンバーであるE2F3dはミトコンドリアに局在する2016

    • Author(s)
      荒木啓吾、芳田亮輔、大谷清
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県、横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] がん細胞に特異的に存在する制御を外れたE2F活性は自殺遺伝子のがん細胞特異的発現に有用である2016

    • Author(s)
      倉吉健太、大谷清
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県、横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] Utility of an artificial promoter, ERE73s-ARF core, for driving suicide gene expression specifically in cancer cells2016

    • Author(s)
      倉吉健太、大谷清
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県、横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] DDX5 promotes ARF gene expression and apoptosis induced by deregulated E2F12016

    • Author(s)
      Kurayoshi K and Ohtani K
    • Organizer
      AACR Annual Meeting 2016
    • Place of Presentation
      Ernest N. Morial Convention Center (New Orleans, USA)
    • Year and Date
      2016-04-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] DDX5はpRBの制御を外れた転写因子E2F1の転写活性化能を増強する2015

    • Author(s)
      芳田亮輔、西淵剛平、中山潤一、大谷清
    • Organizer
      第38回 日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(兵庫県・神戸市)
    • Year and Date
      2015-12-03
    • Related Report
      2015 Research-status Report
  • [Presentation] 転写因子E2F1のARFプロモーター活性化能に関わるリン酸化部位の検索2015

    • Author(s)
      脇田かおり、大谷清
    • Organizer
      第38回 日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(兵庫県・神戸市)
    • Year and Date
      2015-12-03
    • Related Report
      2015 Research-status Report
  • [Presentation] ヒトT細胞白血病ウイルスの転写制御因子TaxによるCARM1遺伝子の発現誘導は、Taxによる標的遺伝子発現と細胞周期進行に貢献する2015

    • Author(s)
      好川翔平、大谷清
    • Organizer
      第38回 日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(兵庫県・神戸市)
    • Year and Date
      2015-12-03
    • Related Report
      2015 Research-status Report
  • [Presentation] PI3K経路は制御を外れたE2F1によるBimおよびARF遺伝子の発現誘導を抑制しない2015

    • Author(s)
      倉吉健太、大谷清
    • Organizer
      第38回 日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(兵庫県・神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] PI3K経路はE2FによるBimとARF遺伝子の発現誘導を阻害しない2015

    • Author(s)
      倉吉健太、大谷清
    • Organizer
      第74回 日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県・名古屋市)
    • Year and Date
      2015-10-10
    • Related Report
      2015 Research-status Report
  • [Book] Gene Expression and Regulation in Mammalian Cells - Transcription Toward the Establishment of Novel Therapeutics2018

    • Author(s)
      Kenta Kurayoshi, Eiko Ozono, Ritsuko Iwanaga, Andrew P. Bradford, Hideyuki Komori, Keigo Araki and Kiyoshi Ohtani
    • Total Pages
      27
    • Publisher
      InTech Open Access Publisher
    • ISBN
      9789535138686
    • Related Report
      2017 Annual Research Report

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

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