A functional proteomics approarch to mechanism of radiation sensitivity.

• Project/Area Number: 26461880
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: The 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: ¥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)
• Keywords: Proteomics / 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.

Research Products

• [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
  • 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
  • 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
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] PI-3K/mTOR pathway inhibition overcomes radioresitance via suppression of the HIF1-alpha/VEGF pathway in endometrial cancer (2015)
  • 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
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] PI-3K/mTOR pathway inhibition overcomes radioresistance via suppression of the HIF1-alpha/VEGF pathway in endometrial cancer (2015)
  • 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
  • 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
  • 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
• [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
• [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
• [Presentation] Multiple roles of STK38 in DNA damage responses (2015)
  • 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
  • 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
• [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
• [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