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Control of transcription factors and epigenetic factors via nuclear transport and its application to targeted therapy

Research Project

Project/Area Number 26280108
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Life / Health / Medical informatics
Research InstitutionNihon University

Principal Investigator

KANEKO Hiroki  日本大学, 文理学部, 上席研究員 (10349946)

Co-Investigator(Renkei-kenkyūsha) YONEDA Yoshihiro  医療基盤・健康・栄養研究所, 研究所長 (80191667)
YASUHARA Noriko  日本大学, 文理学部, 准教授 (90423152)
KONDOU Yutaka  名古屋大学, 大学院医学系研究科, 教授 (00419897)
OKUZAKI Daisuke  大阪大学, 微生物病研究所, 助教 (00346131)
Research Collaborator YAMAGISHI Ryosuke  
SHIMADA Jiro  
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Fiscal Year 2016: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2015: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2014: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Keywords核輸送 / 生体生命情報学 / 発現制御 / インポーチン / 転写因子 / エピジェネティクス / 計算構造生物学 / NLS / 核輸送制御
Outline of Final Research Achievements

To contribute to the elucidation of nuclear transport mechanisms we have (1) predicted the structure of the complex formed between transcription factor Oct3/4 and importin α; (2) performed a comprehensive analysis of the dynamic structure of nuclear localization signals (NLS); and (3) elucidated the release mechanism of cargo proteins from importin α. In addition, we identified two NLS sites in epigenetic factor EZH2 and inferred its nuclear import mechanism. Furthermore, we designed and developed chemical compounds that inhibit the formation of the PRC2 complex including EZH2 and then explored their potential for the targeted therapy of lymphomas and other cancers.

Report

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

    (14 results)

All 2017 2016 2015 2014 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 4 results,  Acknowledgement Compliant: 3 results) Presentation (5 results) (of which Invited: 1 results) Remarks (3 results)

  • [Journal Article] Structural and mechanistic insights into nuclear transport and delivery of the critical pluripotency factor Oct4 to DNA2017

    • Author(s)
      Takahide Okuyama, Ryosuke Yamagishi, Jiro Shimada, Masaaki Ikeda, Yayoi Maruoka, Hiroki Kaneko
    • Journal Title

      Journal of Biomolecular Structure and Dynamics

      Volume: 印刷中 Issue: 3 Pages: 767-778

    • DOI

      10.1080/07391102.2017.1289124

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Homozygous EDNRB Mutation in a Patient with Waardenburg Syndrome Type 12017

    • Author(s)
      Noriko Morimoto, Hideki Mutai, Kazunori Namba, Hiroki Kaneko, Rika Kosaki, Tatsuo Matsunaga
    • Journal Title

      Auris Nasus Larynx

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Data from comprehensive analysis of nuclear localization signals2016

    • Author(s)
      Ryosuke Yamagishi, Hiroki Kaneko
    • Journal Title

      Data in Brief

      Volume: 6 Pages: 200-203

    • DOI

      10.1016/j.dib.2015.11.064

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Molecular impairment mechanisms of novel OPA1 mutations predicted by molecular modeling in patients with autosomal dominant optic atrophy and auditory neuropathy spectrum disorder2016

    • Author(s)
      Kazunori Namba, Hideki Mutai, Yoichiro Takiguchi, Hirotaka Yagi, Takahide Okuyama, Shuntaro Oba, Ryosuke Yamagishi, Hiroki Kaneko, Tomoko Shintani, Kimitaka Kaga, Tatsuo Matsunaga
    • Journal Title

      Otology & Neurotology

      Volume: 37 Issue: 4 Pages: 394-402

    • DOI

      10.1097/mao.0000000000000978

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comprehensive analysis of the dynamic structure of nuclear localization signals2015

    • Author(s)
      Ryosuke Yamagishi, Takahide Okuyama, Shuntaro Oba, Jiro Shimada, Shigeru Chaen, Hiroki Kaneko
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 4 Pages: 392-396

    • DOI

      10.1016/j.bbrep.2015.11.001

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A mutation in the heparin-binding site of noggin as a novel mechanism of proximal symphalangism and conductive hearing loss2014

    • Author(s)
      Masuda S., Namba K., Mutai H., Usui S., Miyanaga Y., Kaneko H., Matsunaga T.
    • Journal Title

      Biochem Biophys Res Comm

      Volume: 447 Issue: 3 Pages: 196-502

    • DOI

      10.1016/j.bbrc.2014.04.015

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 核移行シグナルNLSの動的構造に関する網羅的解析: NLSの天然変性領域としての可能性2016

    • Author(s)
      山岸 良介 ,金子 寛生
    • Organizer
      第39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
      2016-12-01
    • Related Report
      2016 Annual Research Report
  • [Presentation] がん細胞におけるEZH2の細胞内局在制御機構の解明2015

    • Author(s)
      趙 娟、畑中 彬良、勝島 啓佑、大岡 史治、出口 彰一、市村 典久、金子 寛生、新城 恵子、近藤 豊
    • Organizer
      第9回日本エピジェネティクス研究会年会
    • Place of Presentation
      一橋講堂
    • Year and Date
      2015-05-25
    • Related Report
      2015 Annual Research Report
  • [Presentation] 核輸送タンパク質と相互作用することにより核輸送を制御する分子の探索2014

    • Author(s)
      山岸 良介 , 奥山 隆英 , 島田 次郎 , 大庭 俊太朗 , 茶圓 茂 , 安原 徳子 , 米田 悦啓 , 金子 寛生
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] 転写因子と核内輸送因子の複合体構造の予測2014

    • Author(s)
      奥山隆英 、山岸良介、島田次郎、安原徳子、米田悦啓、金子寛生
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] 核輸送による遺伝子発現制御と細胞運命決定のメカニズム2014

    • Author(s)
      安原徳子、山岸良介、金子寛生、米田悦啓
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-16
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Remarks] 国立研究開発法人医薬基盤・健康・栄養研究所 細胞核輸送ダイナミクスプロジェクト

    • URL

      http://www.nibiohn.go.jp/activities/nuclear-transport.html

    • Related Report
      2016 Annual Research Report
  • [Remarks]

    • URL

      http://www.oka-lab.info/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 金子研究室

    • URL

      http://w3p.phys.chs.nihon-u.ac.jp/~kaneko/

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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