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A functional proteomics approarch to mechanism of radiation sensitivity.

Research Project

Project/Area Number 26461880
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Radiation science
Research InstitutionThe University of Tokyo

Principal Investigator

Enomoto Atsushi  東京大学, 大学院医学系研究科(医学部), 講師 (20323602)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsProteomics / STK38 / Radiation sensitivity / DNA damage responses / DNA損傷応答 / プロテオーム / リン酸化 / DNA損傷シグナル / DNA二重鎖切断 / 放射線感受性 / 放射線応答
Outline of Final Research Achievements

STK38 (serine/threonine kinase 38), also known as NDR1 (nuclear Dbf2-related 1, is a serine/threonine protein kinase belonging to a subclass of the protein kinase A (PKA)/PKG/PKC-like (AGC) family, which includes cAMP-dependent kinase, protein kinase B, and protein kinase C. Knockdown of STK38 enhacnes cellular radio-sensitivity. However, its substrates and downstream signaling pathways remain to be determined. The fuction proteomics approarch revealved that STK38 endogenouly interact with CDC25A and that STK38 directly regulates CDC25A’s stability by phosphorylating Ser-76.Moreover, the STK38/CDC25A signaling module is demonstrated to be required to regulate the DNA-damage-induced G2/M checkpoint. Together, the results suggest thatthe STK38 knockdown-mediated radiosensitization may be due, at least in part, to impaired DNA damage-induced G2 arrest resulting from defective CDC25A degradation.

Report

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

    (13 results)

All 2017 2016 2015 2014

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Acknowledgement Compliant: 3 results,  Open Access: 1 results) Presentation (7 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Bisdemethoxycurcumin enhances X-ray-induced apoptosis possibly through p53/Bcl-2 pathway.2017

    • Author(s)
      A. Enomoto, J. Yamada, A. Morita, and K. Miyagawa.
    • Journal Title

      Mutat. Res.

      Volume: 815 Pages: 1-5

    • DOI

      10.1016/j.mrgentox.2016.12.005

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Extremotolerant tardigrade genome and improved radiotolerance of human cultured cells by tardigrade-unique protein.2016

    • Author(s)
      Hashimoto T, Horikawa DD, Saito Y, Kuwahara H, Kozuka-Hata H, Shin-I T, Minakuchi Y, Ohishi K, Motoyama A, Aizu T, Enomoto A, Kondo K, Tanaka S, Hara Y, Koshikawa S, Sagara H, Miura T, Yokobori S, Miyagawa K, Suzuki Y, Kubo T, Oyama M, Kohara Y, Fujiyama A, Arakawa K, Katayama T, Toyoda A and Kunieda T
    • Journal Title

      Nature Communications

      Volume: 7 Issue: 1 Pages: 12808-12808

    • DOI

      10.1038/ncomms12808

    • NAID

      120005971035

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serine-Threonine Kinase 38 regulates CDC25A stability and the DNA damage-induced G2/M checkpoint.2015

    • Author(s)
      T. Fukasawa, A. Enomoto, and K. Miyagawa
    • Journal Title

      Cellular Signalling

      Volume: 27 Pages: 1569-1575

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] PI-3K/mTOR pathway inhibition overcomes radioresitance via suppression of the HIF1-alpha/VEGF pathway in endometrial cancer2015

    • Author(s)
      A. Miyasaka, K. Oda, Y. Ikeda, O. Wada-Hiraike, T. Kashiyama, A. Enomoto, et al.,
    • Journal Title

      Gynecologic Oncology

      Volume: 138 Pages: 174-180

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] PI-3K/mTOR pathway inhibition overcomes radioresistance via suppression of the HIF1-alpha/VEGF pathway in endometrial cancer2015

    • Author(s)
      A. Miyasaka, K. Oda, Y. Ikeda, K. Sone, T. Fukuda, K. Inaba, C. Makii, A. Enomoto, N. Hosoya, M. Tanikawa, Y. Uehara, T. Arimoto, H. Kuramoto, O. Wada-Hiraike, K. Miyagawa, T. Yano, K. Kawana, Y. Osuga, T. Fujii
    • Journal Title

      Gynecologic Oncology

      Volume: 印刷中

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] HSP90阻害剤の抗腫瘍メカニズムと放射線増感への応用2014

    • Author(s)
      榎本 敦
    • Journal Title

      放射線生物研究

      Volume: 49 Pages: 235-247

    • NAID

      40020222321

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] SUMO化によるSTK38の活性制御と放射線感受性への寄与2016

    • Author(s)
      榎本 敦、深澤 毅倫、宮川 清
    • Organizer
      日本放射線影響学会第59回大会
    • Place of Presentation
      JMSアステールプラザ (広島県広島市)
    • Year and Date
      2016-10-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] 古くて新しいクルクミンの放射線増感メカニズム2016

    • Author(s)
      榎本 敦
    • Organizer
      第18回癌治療増感研究シンポジウム
    • Place of Presentation
      奈良県文化会館(奈良県奈良市)
    • Year and Date
      2016-02-04
    • Related Report
      2015 Research-status Report
  • [Presentation] DNA損傷によって誘発されるSTK38/NDR1の翻訳後修飾とその活性制御における意義2015

    • Author(s)
      榎本 敦
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2015-12-03
    • Related Report
      2015 Research-status Report
  • [Presentation] Multiple roles of STK38 in DNA damage responses2015

    • Author(s)
      榎本 敦
    • Organizer
      International Congress of Radiation Research 2015
    • Place of Presentation
      京都国際会議場(京都府左京区)
    • Year and Date
      2015-05-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] DNA損傷誘発細胞周期制御におけるSTK38の役割と増感への応用2015

    • Author(s)
      榎本 敦
    • Organizer
      第17回癌治療増感研究シンポジウム
    • Place of Presentation
      奈良県文化会館 (奈良県奈良市)
    • Year and Date
      2015-02-07
    • Related Report
      2014 Research-status Report
  • [Presentation] 酸化ストレスにおけるSTK38/NDR1の役割2014

    • Author(s)
      榎本 敦
    • Organizer
      第37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
      2014-11-25
    • Related Report
      2014 Research-status Report
  • [Presentation] DNA損傷応答におけるSTK38の役割2014

    • Author(s)
      榎本 敦
    • Organizer
      日本放射線影響学会第57回大会
    • Place of Presentation
      鹿児島県民交流センター (鹿児島県鹿児島市)
    • Year and Date
      2014-10-01
    • Related Report
      2014 Research-status Report

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

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