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2012 Fiscal Year Final Research Report

A new method to evaluate the function of mitotic kinases by monitoring chromosome dynamics

Research Project

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Project/Area Number 23651243
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Chemical biology
Research InstitutionJapanese Foundation For Cancer Research

Principal Investigator

HIROTA Toru  公益財団法人がん研究会, がん研究所実験病理部, 部長 (50421368)

Co-Investigator(Renkei-kenkyūsha) ABE Yusuke  公益財団法人がん研究会, がん研究所・実験病理部, 博士研究員 (50615896)
UCHIDA Kazuhiko  公益財団法人がん研究会, がん研究所・実験病理部, 博士研究員 (40380555)
SHINDO Norihisa  公益財団法人がん研究会, がん研究所・実験病理部, 博士研究員 (00512253)
KUMADA Kazuki  公益財団法人がん研究会, がん研究所・実験病理部, 博士研究員 (10370149)
Project Period (FY) 2011 – 2012
KeywordsM期 / 染色体 / がん細胞 / キナーゼ阻害薬
Research Abstract

Mitotic kinases play crucial roles in separating chromosomes correctly and safely as cells divide. Dysfunction of mitotic kinases therefore causes defective chromosome movements and segregation. In this study, we aimed to develop an assay to indicate cryptic dysfunction of mitotic kinases by monitoring chromosome behavior during mitosis, which is otherwise difficult to detect in conventional means. We found that increasing dose of specific inhibitors of mitotic kinases, caused abnormal chromosomal movements progressively. This what we called the stepwise-challenging assay was then used to address the function of mitotic kinases in several cancer cells that are known to have chromosomal instability

  • Research Products

    (41 results)

All 2013 2012 2011 Other

All Journal Article (5 results) Presentation (28 results) Book (6 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Separase sensor reveals dual roles for separase coordinating cohesin cleavage and cdk1 inhibition2012

    • Author(s)
      Shindo, N., Kumada, K., *Hirota, T
    • Journal Title

      Dev. Cell

      Volume: 23 Pages: 112-123

  • [Journal Article] HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle2012

    • Author(s)
      Deardorff MA., Bando, M., Nakato, R., Watrin, E., Itoh, T., Minamino, M.,Saitoh,K., Komata, M., Katou, Y., Clark, D., Cole, KE., De Baere, E., Decroos, C., Di Donato, N., Ernst, S., Francey, LJ., Gyftodimou, Y., Hirashima, K., Hullings, M., Ishikawa, Y., Jaulin, C., Kaur, M., Kiyono, T., Lombardi, PM., Magnaghi-Jaulin, L., Mortier, GR., Nozaki, N., Petersen, MB., Seimiya, H., Siu, VM., Suzuki, Y., Takagaki, K., Wilde, JJ., Willems, PJ, Prigent, C., Gillessen-Kaesbach, G., Christianson, DW., Kaiser, FJ., Jackson, LG., Hirota, T., Krantz ID., *Shirahige K
    • Journal Title

      Nature

      Volume: 489 Pages: 313-317

  • [Journal Article] The initial phase of chromosome condensation requires Cdk1-mediated phosphorylation of the CAP-D3 subunit of condensin II2011

    • Author(s)
      Abe, S., Nagasaka, K., Hirayama, Y., Kozuka-Hata, H., Oyama, M., Aoyagi, Y., Obuse, C., and *Hirota, T
    • Journal Title

      Genes Dev

      Volume: 25 Pages: 863-874

  • [Journal Article] CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-microtubule attachment2011

    • Author(s)
      Ito, G., Kanno, S., Uchida, K.S.K, Chiba, S., Sugino, S., Watanabe, K., Mizuno, K., Yasui, A., Hirota, T., and *Tanaka, K
    • Journal Title

      EMBO J

      Volume: 30 Pages: 130-144

  • [Journal Article] Differential control of Eg5 dependent centrosome separation by Plk1 and Cdk12011

    • Author(s)
      Smith, E., Hegarat, N., Vesely, C., Roseboom, I., Streicher, H., Straatman, K., Flynn, H., Skehel, M., Hirota, T., Kuriyama, R., *Hochegger, H
    • Journal Title

      EMBO J

      Volume: 30 Pages: 2233-2245

  • [Presentation] How cells ensure separation of sister chromatids in mitosis2013

    • Author(s)
      Hirota, T
    • Organizer
      International Symposium on Molecular Medicine
    • Place of Presentation
      (Suwon, Korea)
    • Year and Date
      2013-02-28
  • [Presentation] M期プロテアーゼ・セパレースの活性プローブによって分かったこと2013

    • Author(s)
      広田 亨
    • Organizer
      東京理科大学先端生命研・水曜セミナー
    • Place of Presentation
      (野田)
    • Year and Date
      2013-01-30
  • [Presentation] How cells ensure separation of sister chromatids in mitosis2012

    • Author(s)
      Hirota, T
    • Organizer
      Jacques Monad Conference "Cell cycle"
    • Place of Presentation
      (Roscoff, France)
    • Year and Date
      20120905-09
  • [Presentation] 染色体分離を決行するM期プロテアーゼ・セパレースの活性制御2012

    • Author(s)
      広田 亨
    • Organizer
      特定領域研究「細胞増殖制御」終了シンポジウム
    • Place of Presentation
      (大岡山)
    • Year and Date
      20120830-31
  • [Presentation] How cells ensure trigger chromosome assembly in cells entering mitosis2012

    • Author(s)
      Hirota, T
    • Organizer
      Symposium Proteolysis and Cohesion
    • Place of Presentation
      (Vienna, Austria)
    • Year and Date
      20120823-24
  • [Presentation] Dual functions of separase ensure switch-like initiation of anaphase2012

    • Author(s)
      Hirota, T
    • Organizer
      Joint Spring Meeting of BSCB/BSCB/JSDB
    • Place of Presentation
      (Coventry, UK)
    • Year and Date
      20120415-18
  • [Presentation] アナログ感受性変異体によるGreatwallキナーゼの機能解析2012

    • Author(s)
      阿部優介、広田 亨
    • Organizer
      第29回染色体ワークショップ
    • Place of Presentation
      (秋保温泉)
    • Year and Date
      20120125-27
  • [Presentation] Separase の自己切断による染色体分配制御2012

    • Author(s)
      熊田和貴、広田 亨
    • Organizer
      第29回染色体ワークショップ
    • Place of Presentation
      (秋保温泉)
    • Year and Date
      20120125-27
  • [Presentation] Separase は染色体分離において一人二役を果たす2012

    • Author(s)
      進藤軌久、広田 亨
    • Organizer
      第29回染色体ワークショップ
    • Place of Presentation
      (秋保温泉)
    • Year and Date
      20120125-27
  • [Presentation] Consecutive functions of separase ensure the chromosome segregation switch2012

    • Author(s)
      Hirota, T
    • Organizer
      Seminar at Research Institute of Genetics and Development
    • Place of Presentation
      (Rennes, France)
    • Year and Date
      2012-09-04
  • [Presentation] How cells ensure separation of sister chromatids in mitosis2012

    • Author(s)
      Hirota, T
    • Organizer
      Seminar at Oxford University Dunn School of Pathology
    • Place of Presentation
      (Oxford, UK)
    • Year and Date
      2012-04-19
  • [Presentation] How cells ensure separation of sister chromatids in mitosis2012

    • Author(s)
      Hirota, T
    • Organizer
      Seminar at Cancer Research UK London Research Insitute
    • Place of Presentation
      (London, UK)
    • Year and Date
      2012-04-18
  • [Presentation] How cells ensure separation of sister chromatids in mitosis2012

    • Author(s)
      Hirota, T
    • Organizer
      Seminar at Imperial College London
    • Place of Presentation
      (London, UK)
    • Year and Date
      2012-04-13
  • [Presentation] がん細胞における異数性の発生要因を考える2012

    • Author(s)
      広田 亨
    • Organizer
      第28回新潟県立中央病院集談会・特別講演
    • Place of Presentation
      (上越)
    • Year and Date
      2012-03-02
  • [Presentation] Does the spindle-assembly checkpoint monitor the presence of tension?2011

    • Author(s)
      Uchida, K.S.K., Hirota, T
    • Organizer
      第30回日本分子生物学会.ワークショップ
    • Place of Presentation
      (横浜)
    • Year and Date
      20111213-16
  • [Presentation] Probing separase activity reveals its switch-like activation at the metaphase-to- anaphase transition2011

    • Author(s)
      Hirota, T
    • Organizer
      第30回日本分子生物学会.シンポジウム
    • Place of Presentation
      (横浜)
    • Year and Date
      20111213-16
  • [Presentation] Dual role of separase during the metaphase-to-anaphase transition ensures chromosome segregation in mammalian cells2011

    • Author(s)
      Shindo, N., Hirota, T
    • Organizer
      Annual meeting of American Society of Cell Biology
    • Place of Presentation
      (Denver)
    • Year and Date
      20111203-09
  • [Presentation] Probing separase activity reveals its switch-like activation at the metaphase-to- anaphase transition2011

    • Author(s)
      Hirota, T
    • Organizer
      The MEXT Priority Research International Symposium "Cell Division"
    • Place of Presentation
      (Hakone)
    • Year and Date
      20110629-0701
  • [Presentation] Probing separase activity reveals its switch-like activation at the metaphase-to- anaphase transition2011

    • Author(s)
      Hirota, T
    • Organizer
      The 2nd Dynamic Kinetochore Workshop
    • Place of Presentation
      (Vienna)
    • Year and Date
      20110615-18
  • [Presentation] がん細胞における異数性の発生要因を考える.要望講演2011

    • Author(s)
      広田 亨
    • Organizer
      第52回日本臨床細胞学会総会
    • Place of Presentation
      (福岡)
    • Year and Date
      20110520-22
  • [Presentation] How chromosome assembly is triggered in cells entering mitosis2011

    • Author(s)
      Hirota, T
    • Organizer
      6th UK-Japan Cell Cycle Meeting
    • Place of Presentation
      (Windermere)
    • Year and Date
      20110410-13
  • [Presentation] How mitotic kinases control chromosome segregation2011

    • Author(s)
      Hirota, T
    • Organizer
      熊本大学GCOE・リエゾンラボ研究会
    • Place of Presentation
      (熊本)
    • Year and Date
      2011-11-02
  • [Presentation] 染色体分離の正確性を保証するメカニズム2011

    • Author(s)
      広田 亨
    • Organizer
      ケミカルバイオロジー勉強会・理化学研究所
    • Place of Presentation
      (和光)
    • Year and Date
      2011-10-26
  • [Presentation] Heterochromatin protein 1 is an essential component of the chromosomal passenger complex to prevent mis- segregation of chromosomes2011

    • Author(s)
      Hirota, T
    • Organizer
      平成23年度遺伝研研究会「クロマチンダイナミクスの分子機構」
    • Place of Presentation
      (三島)
    • Year and Date
      2011-10-20
  • [Presentation] The switch-like activation of separase ensures chromosome segregation2011

    • Author(s)
      Hirota, T
    • Organizer
      The GCOE International Workshop "Mitosis"
    • Place of Presentation
      (Yokohama)
    • Year and Date
      2011-07-04
  • [Presentation] 染色体分離の同期性を保証するメカニズム2011

    • Author(s)
      広田 亨
    • Organizer
      北海道大学大学院・先端生命科学研究院・分子生物学特別セミナー
    • Place of Presentation
      (札幌)
    • Year and Date
      2011-06-24
  • [Presentation] How chromosome assembly is triggered in cells entering mitosis2011

    • Author(s)
      Hirota, T
    • Organizer
      Impromptu Seminar at the IMP.
    • Place of Presentation
      (Vienna)
    • Year and Date
      2011-04-14
  • [Presentation] Heterochromatin protein 1 is an essential component of the chromosomal passenger complex to prevent missegregation of chromosomes

    • Author(s)
      Hirota, T
  • [Book] 総説「細胞分裂の仕組みに迫る―染色体分離のキー酵素separaseの活性の可視化と作用機序の解明」バイオサイエンスとインダストリー2013

    • Author(s)
      進藤軌久、広田 亨
  • [Book] 総説「Greatwallによるリン酸化バランス調節に基づくM期開始制御」 実験医学増刊号・ヒトと医学のステージへ拡大する細胞周期2013

    • Author(s)
      阿部優介、広田 亨
    • Publisher
      羊土社
  • [Book] Review. Handbook of Proteolytic Enzymes. Third Edition, Edited by Rawlings and Salvesen, Elsevier.2012

    • Author(s)
      Kumada, K., and *Hirota, T
    • Publisher
      Separase
  • [Book] 記事「がん医療を拓く―ふぞろいを狙い撃つ」2012

    • Author(s)
      広田 亨
    • Publisher
      ロハスメディカル
  • [Book] 総説「バイオセンサーにより明らかにされた染色体分離におけるセパラーゼの異なる2つの役割」2012

    • Author(s)
      進藤軌久、広田 亨
    • Publisher
      ライフサイエンス新着論文レビュー
  • [Book] Encyclopedia of Life Sciences, John Wiley & Sons, Ltd2011

    • Author(s)
      Nagasaka, K., Gallego-Paez, L.M., * Hirota, T
    • Publisher
      Mitosis and Meiosis: Molecular Control of Chromosome Separation. Review
  • [Remarks] ホームページ

    • URL

      http://www.jfcr.or.jp/tci/exppathol/index.html

  • [Patent(Industrial Property Rights)] セパレース・バイオセンサー2012

    • Inventor(s)
      広田亨、進藤軌久、熊田和貴
    • Industrial Property Rights Holder
      公益財団法人がん研究会
    • Industrial Property Number
      仮出願 61/670306
    • Filing Date
      20120700
    • Overseas

URL: 

Published: 2014-08-29   Modified: 2014-10-02  

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