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Molecular mechanisms of bipolar spindle assembly in the absence of Kinesin-5/Cut7

Research Project

Project/Area Number 16K07694
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied biochemistry
Research InstitutionHiroshima University

Principal Investigator

Yukawa Masashi  広島大学, 先端物質科学研究科, 特任助教 (50403605)

Research Collaborator TODA takashi  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords染色体分配 / 紡錘体 / 微小管 / キネシンモーター / 5型キネシン / 14型キネシン / 微小管ポリメラーゼ / 有糸分裂 / 5型キネシン / 14型キネシン / 6型キネシン / キネシン / 分裂酵母
Outline of Final Research Achievements

The assembly of a bipolar spindle is necessary to ensure the fidelity of chromosome segregation. In all eukaryotes, spindle formation is driven by the plus-end directed motor kinesin-5. Inactivation of this kinesin causes mitotic arrest with monopolar spindles. Interestingly, simultaneous inactivation of the minus-end directed kinesin-14 restores cell viability in fission yeast. Apparent normal spindle assembly in the absence of both kinesin-5 and kinesin-14 has highlighted the existence of other hitherto unknown factors by which to establish and maintain mitotic bipolar spindles. To uncover these molecules, we have conducted two complementary independent genetic screens. Consequently, we have succeeded in identifying kinesins, microtubule-associated proteins and their regulators.

Academic Significance and Societal Importance of the Research Achievements

本研究成果により同定に成功した新規紡錘体形成因子はいずれも酵母からヒトまで進化上高度に保存されていることから、高等生物においても類似した紡錘体形成機構が存在すると考えられる。また、これらの新規紡錘体形成因子を阻害することにより、がん細胞の増殖を抑えることができると考えられ、副作用の少ないがん治療薬の開発に繋がることが期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (34 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (5 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 5 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (25 results) (of which Int'l Joint Research: 3 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] 中央医薬品研究所(CDRI)(インド)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] カリフォルニア大学サンディエゴ校(米国)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Fission yeast cells overproducing HSET/KIFC1 provides a useful tool for identification and evaluation of human kinesin-14 inhibitors2018

    • Author(s)
      Yukawa Masashi、Yamauchi Tomoaki、Kurisawa Naoaki、Ahmed Shakil、Kimura Ken-ichi、Toda Takashi
    • Journal Title

      Fungal Genetics and Biology

      Volume: 116 Pages: 33-41

    • DOI

      10.1016/j.fgb.2018.04.006

    • NAID

      120006800807

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Suppressor Analysis Uncovers That MAPs and Microtubule Dynamics Balance with the Cut7/Kinesin-5 Motor for Mitotic Spindle Assembly in Schizosaccharomyces pombe2018

    • Author(s)
      Yukawa Masashi、Yamada Yusuke、Toda Takashi
    • Journal Title

      G3 (Genes|Genomes|Genetics)

      Volume: 9 Issue: 1 Pages: 269-280

    • DOI

      10.1534/g3.118.200896

    • NAID

      120006784517

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Two spatially distinct kinesin-14 proteins, Pkl1 and Klp2, generate collaborative inward forces against kinesin-5 Cut7 in S. pombe.2018

    • Author(s)
      Masashi Yukawa, Yusuke Yamada, Tomoaki Yamauchi, and Takashi Toda
    • Journal Title

      Journal of Cell Science

      Volume: 131 Issue: 1 Pages: 1-11

    • DOI

      10.1242/jcs.210740

    • NAID

      120006784518

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A microtubule polymerase cooperates with the kinesin-6 motor and a microtubule cross-linker to promote bipolar spindle assembly in the absence of kinesin-5 and kinesin-14 in fission yeast.2017

    • Author(s)
      Masashi Yukawa, Tomoki Kawakami, Masaki Okazaki, Kazunori Kume, Ngang Heok Tang, and Takashi Toda
    • Journal Title

      Molecular Biology of the Cell

      Volume: 28 Issue: 25 Pages: 3647-3659

    • DOI

      10.1091/mbc.e17-08-0497

    • NAID

      120006784519

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An unconventional interaction between Dis1/TOG and Mal3/EB1 in fission yeast promotes the fidelity of chromosome segregation2016

    • Author(s)
      Matsuo, Y., Maurer, S. P., Yukawa, M., Zakian, S., Singleton, M. R., Surrey, T. and Toda,
    • Journal Title

      J Cell Sci

      Volume: 129 Issue: 24 Pages: 4592-4606

    • DOI

      10.1242/jcs.197533

    • NAID

      120006811255

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 分裂酵母の新規RNA結合タンパク質Nrp1の機能解析2019

    • Author(s)
      湯川格史, 山田侑亮, 大石充輝, 登田 隆
    • Organizer
      先進ゲノム解析研究推進プラットフォーム拡大班会議
    • Related Report
      2018 Annual Research Report
  • [Presentation] Screening for anti-tumor compounds using HSET-overproduction fission yeast and isolated kolavenic acid analog from Solidago altissima.2018

    • Author(s)
      Kurisawa N., Koshino H.,Yukawa M., Toda T., Kimura K
    • Organizer
      International Symposium on Innovative Agriculture and Fishery(ISIAF 2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Exploring the molecular pathways leading to bipolar spindle formation.2018

    • Author(s)
      Toda T., Okazaki M., Yamauchi T., Yamada Y., Kawakami T., Teratani Y., Oishi M., Yukawa M.
    • Organizer
      Joint Annual Meeting of 51st JSDB and 70th JSCB
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒトキネシン-14(HSET)過剰発現分裂酵母株を用いて単離されたkolavenic acid analogの生物活性2018

    • Author(s)
      栗澤尚瑛、湯川格史、越野広雪、登田 隆、木村賢一
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 分裂酵母を用いたヒト14型キネシン阻害剤の探索2018

    • Author(s)
      登田 隆, Ahmed Shakil、栗澤尚瑛,木村賢一, 湯川格史
    • Organizer
      第51回 酵母遺伝学フォーラム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 分裂酵母6型キネシンモーターKlp9の機能ドメインと細胞周期制御2018

    • Author(s)
      湯川格史、登田 隆
    • Organizer
      第51回 酵母遺伝学フォーラム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 分裂酵母Kinesin-5/Cut7と拮抗的に機能する微小管関連因子群の同定と解析2018

    • Author(s)
      山田侑亮、湯川格史、登田 隆
    • Organizer
      第51回 酵母遺伝学フォーラム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 双極性紡錘体形成における力発生装置としての微小管ポリメラーゼ複合体Alp7-Alp14の新規機能2018

    • Author(s)
      河上友基, 湯川格史、登田 隆
    • Organizer
      第51回 酵母遺伝学フォーラム
    • Related Report
      2018 Annual Research Report
  • [Presentation] PCR法を用いた分裂酵母5型キネシンcut7変異体の包括的分離と解析2018

    • Author(s)
      寺谷康宏, 湯川格史、登田 隆
    • Organizer
      第51回 酵母遺伝学フォーラム
    • Related Report
      2018 Annual Research Report
  • [Presentation] M期紡錘体形成に必須な分裂酵母5型キネシンcut7変異を抑制するRNA結合タンパク質遺伝子nrp1の解析2018

    • Author(s)
      大石充輝, 湯川格史、登田 隆
    • Organizer
      第51回 酵母遺伝学フォーラム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 分裂酵母5型キネシンcut7変異を抑圧する多コピーサプレッサーの取得と解析2018

    • Author(s)
      武藤 慧、湯川格史、登田 隆
    • Organizer
      第36回イーストワークショップ
    • Related Report
      2018 Annual Research Report
  • [Presentation] 分裂酵母を利用した新規生理活性物質の探索と解析2018

    • Author(s)
      森山 亮、稲田彩花、湯川格史、登田 隆
    • Organizer
      第36回イーストワークショップ
    • Related Report
      2018 Annual Research Report
  • [Presentation] 染色体分配に必須な紡錘体微小管構造を規定するキネシン依存的及び非依存的経路の同定2018

    • Author(s)
      登田 隆, 山田侑亮, 河上友基, 寺谷康宏, 大石充輝, 湯川格史
    • Organizer
      第41回 日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 分裂酵母を用いた抗がん剤シードとなる分子標的阻害物質の新規探索法2018

    • Author(s)
      湯川格史, 栗澤尚瑛, Ahmed Shakil, 木村賢一, 登田 隆
    • Organizer
      第41回 日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 紡錘体微小管形成における14型キネシンファミリータンパク質の役割2018

    • Author(s)
      湯川格史
    • Organizer
      日本農芸化学会2018年度大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 新規紡錘体形成経路の探索2017

    • Author(s)
      湯川格史
    • Organizer
      日本農芸化学会2017年度大会
    • Place of Presentation
      京都女子大学
    • Year and Date
      2017-03-19
    • Related Report
      2016 Research-status Report
  • [Presentation] Assembly of the mitotic bipolar spindle in the absence of kinesin-5 Cut72017

    • Author(s)
      湯川格史
    • Organizer
      The 9th International Fission Yeast Meeting (Pombe2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Kinesin-5に依存しない新規紡錘体形成経路の探索2017

    • Author(s)
      登田 隆
    • Organizer
      第69回日本細胞生物学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 5型キネシンに依存しない新規紡錘体形成経路の探索2017

    • Author(s)
      湯川格史
    • Organizer
      酵母遺伝学フォーラム第50回研究報告会
    • Related Report
      2017 Research-status Report
  • [Presentation] 分裂酵母の微小管ポリメラーゼ複合体Alp7/TACC-Alp14/TOGによる新たな双極性紡錘体形成機構2017

    • Author(s)
      河上友基
    • Organizer
      酵母遺伝学フォーラム第50回研究報告会
    • Related Report
      2017 Research-status Report
  • [Presentation] 分裂酵母Kinesin-5/Cut7の温度感受性変異を抑圧する変異株の解析2017

    • Author(s)
      山田侑亮
    • Organizer
      酵母遺伝学フォーラム第50回研究報告会
    • Related Report
      2017 Research-status Report
  • [Presentation] 5型キネシンを必要としない新規M期紡錘体構造形成経路2017

    • Author(s)
      登田 隆
    • Organizer
      第40回日本分子生物学会年会(2017年度生命科学系学会合同年次大会, ConBio2017)
    • Related Report
      2017 Research-status Report
  • [Presentation] 新規紡錘体形成経路の探索2016

    • Author(s)
      湯川格史
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-12-01
    • Related Report
      2016 Research-status Report
  • [Presentation] 新規紡錘体形成経路の探索2016

    • Author(s)
      湯川格史
    • Organizer
      酵母遺伝学フォーラム第49回研究報告会
    • Place of Presentation
      シーサイドホテル舞子ビラ神戸
    • Year and Date
      2016-09-09
    • Related Report
      2016 Research-status Report
  • [Presentation] 既知のキネシンに依存しない染色体分配機構の解明2016

    • Author(s)
      岡崎雅紀
    • Organizer
      酵母遺伝学フォーラム第49回研究報告会
    • Place of Presentation
      シーサイドホテル舞子ビラ神戸
    • Year and Date
      2016-09-09
    • Related Report
      2016 Research-status Report
  • [Remarks] 【研究成果】染色体の分配装置が形成される新たな仕組みを解明 ―がん治療薬開発の分子標的として期待―

    • URL

      https://www.hiroshima-u.ac.jp/news/42166

    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] キネシン阻害剤、該阻害剤を含む抗癌剤およびキネシン阻害剤のスクリーニング方法2018

    • Inventor(s)
      登田 隆, 湯川格史, 木村賢一, 栗澤尚瑛, 越野広雪
    • Industrial Property Rights Holder
      登田 隆, 湯川格史, 木村賢一, 栗澤尚瑛, 越野広雪
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-087733
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2022-02-21  

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