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Molecular mechanisms of crosstalk between DNA-damage response and signal transduction

Research Project

Project/Area Number 25290044
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Tumor biology
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Kitagawa Masatoshi  浜松医科大学, 医学部, 教授 (50294971)

Co-Investigator(Kenkyū-buntansha) 松本 雅記  九州大学, 生体防御医学研究所, 准教授 (60380531)
Co-Investigator(Renkei-kenkyūsha) NIIDA Hiroyuki  浜松医科大学, 医学部, 准教授 (20336671)
Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2015: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2013: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
KeywordsDNA障害応答 / シグナル伝達 / リン酸化 / DNA損傷応答
Outline of Final Research Achievements

We found that Mig-6, an internal inhibitor of EGFR,is phosphorylated accompanied by EGF stimulation but also UV-irradiation. The results suggest that there is a crosstalk between EGF-signaling and DNA-damage response. Next, we found that HBO1,a histone acetyltransferase, phosphorylated Ser50/Ser53 of HBO1 by ATR after UV irradiation. HBO1 is ubiquitylated by CUL4-DDB1/DDB2 and degraded 6h after UV-irradiation. Moreover, we found that HBO1 participated in nucleotide excision repair(NAR). UV-DNA-damege induced phosphorylation of HBO1 promoted acetylation of histone H3 to induce structural change of chromatin in the damaged sites. These results suggested that the HBO1-mediated chromatin conformational change promoted recruitment of NER-related factors to enhanced the NER.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (10 results)

All 2015 2014 2013 2012 Other

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results) Presentation (2 results) Remarks (3 results)

  • [Journal Article] UV Damage-Induced Phosphorylation of HBO1 Triggers CRL4DDB2-Mediated Degradation To Regulate Cell Proliferation.2015

    • Author(s)
      Matsunuma R, Niida H, Ohhata T, Kitagawa K, Sakai S, Uchida C, Shiotani B, Matsumoto M, Nakayama KI, Ogura H, Shiiya N, Kitagawa M.
    • Journal Title

      Mol Cell Biol.

      Volume: 36 Issue: 3 Pages: 394-406

    • DOI

      10.1128/mcb.00809-15

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Interaction between RB protein and NuMA is required for proper alignment of spindle microtubules2014

    • Author(s)
      Uchida, C., Hattori, T., Takahashi, H., Yamamoto, N., Kitagawa, M. and Taya, Y.
    • Journal Title

      Genes Cells

      Volume: 19 Issue: 2 Pages: 89-96

    • DOI

      10.1111/gtc.12119

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell cycle regulation by long non-coding RNAs.2013

    • Author(s)
      Kitagawa M, Kitagawa K, Kotake Y, Niida H, Ohhata T.
    • Journal Title

      Cell Mol Life Sci.

      Volume: 24 Issue: 24 Pages: 4785-4794

    • DOI

      10.1007/s00018-013-1423-0

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] YB1 binds to and represses the p16 tumor suppressor gene.2013

    • Author(s)
      Kotake Y, Ozawa Y, Harada M, Kitagawa K, Niida H, Morita Y, Tanaka K, Suda T, Kitagawa M.
    • Journal Title

      Genes Cells.

      Volume: 11 Issue: 11 Pages: 999-1006

    • DOI

      10.1111/gtc.12093

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Roles of the Skp2/p27 axis in the progression of chronic nephropathy2012

    • Author(s)
      Suzuki, S., Ohashi, N. and Kitagawa, M
    • Journal Title

      Cell Mol Life Sci

      Volume: (in press) Issue: 18 Pages: 3277-3289

    • DOI

      10.1007/s00018-012-1232-x

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] A nobel substrate for Fbw7, the tumor suppressive ubiquitin ligase2013

    • Author(s)
      Masatoshi Kitagawa, Kyoko Kitagawa
    • Organizer
      第72回日本癌学会総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] ATM/ATR-dependent phosphorylation dissociates HBO1 from replication origin2013

    • Author(s)
      丹伊田浩行、塩谷文章、松本雅記、西谷秀男、北川雅敏
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Remarks] 国立大学法人浜松医科大学医学部分子生物学講座

    • URL

      https://www.hama-med.ac.jp/uni_education_igakubu_igaku_seika1.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 浜松医科大学・医学部・分子生物学講座

    • URL

      https://www.hama-med.ac.jp/uni_education_igakubu_igaku_seika1.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] 浜松医科大学医学部 分子生物学講座

    • URL

      http://www.hama-med.ac.jp/uni_education_igakubu_igaku_seika1.html

    • Related Report
      2014 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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