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Molecular mechanisms that maintain centrosome integrity by SAPK and mechanisms that regulate PLK4 localization to centrosomes.

Research Project

Project/Area Number 25893039
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field General medical chemistry
Research InstitutionThe University of Tokyo

Principal Investigator

NAKAMURA Takanori  東京大学, 医科学研究所, 助教 (30707576)

Project Period (FY) 2013-08-30 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
KeywordsSAPK / PLK4 / p38 / JNK / 中心体 / p53 / 染色体安定性 / シグナル伝達 / ストレス応答
Outline of Final Research Achievements

Centrosomes function as bipolar mitotic spindles, which are essential to chromosomal equal segregation. Centrosome biogenesis is control by PLK4 and centrosome duplication is tightly regulated to once per cell cycle in normal cells. In contrast, centrosome number is often increased after various stresses in cancer cells. The molecular mechanisms underlying centrosome overduplication process, however, had remained obscure. Recently we reported that the two major stress responsive SAPK pathway and p53 pathway cooperatively PLK4 kinase activity and PLK4-driven centrosome duplication under stress. Moreover, we identify the novel substrate of SAPK in centrosome duplication arrest.
We also identify several proteins, which regulate PLK4 localization to centrosomes.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • Research Products

    (8 results)

All 2015 2014 2013 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (4 results) (of which Invited: 2 results) Remarks (2 results)

  • [Journal Article] MCRIP1, an ERK substrate, mediates ERK-induced gene silencing during epithelial-mesenchymal transition by regulating the co-repressor CtBP.2015

    • Author(s)
      Ichikawa K, Kubota Y, Nakamura T, Weng JS, Tomida T, Saito H and Takekawa M.
    • Journal Title

      Molecular Cell

      Volume: 58 Pages: 35-46

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] SAPK pathways and p53 cooperatively regulate PLK4 activity and centrosome integrity under stress.2013

    • Author(s)
      Nakamura, T.
    • Journal Title

      Nature Commun.

      Volume: 4 Issue: 1 Pages: 1775-1775

    • DOI

      10.1038/ncomms2752

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] 癌抑制遺伝子MKK4とp53による中心体数および染色体安定性の保持機構と癌におけるその破綻2015

    • Author(s)
      中村 貴紀、 武川 睦寛
    • Organizer
      日本臨床分子医学会
    • Place of Presentation
      京都
    • Year and Date
      2015-04-10 – 2015-04-11
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Centrosome integrity under stress is maintained by a network of PLK4, p53 and SAPK pathways2014

    • Author(s)
      中村 貴紀、 武川 睦寛
    • Organizer
      細胞生物学会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] ストレス環境下における PLK4、p53、SAPK 経路による中心体保持機構2014

    • Author(s)
      中村 貴紀、 武川 睦寛
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Centrosome integrity under stress is maintained by a network of PLK4, p53 and SAPK pathways2014

    • Author(s)
      中村 貴紀、 武川 睦寛
    • Organizer
      日本分子生物学会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Remarks] ストレス環境下で中心体数と染色体の安定性を保持する仕組み―がん抑制遺伝子MKK4とp53の共同作業―

    • URL

      http://www.ims.u-tokyo.ac.jp/imsut/jp/research/papers/mkk4p53.php

    • Related Report
      2013 Annual Research Report
  • [Remarks] ストレス環境下における中心体数と染色体安定性の保持機構

    • URL

      http://shushoku-signal.com/result/23653187.html

    • Related Report
      2013 Annual Research Report

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Published: 2013-09-12   Modified: 2019-07-29  

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