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Oncogenic mechanisms by nucleoporin

Research Project

Project/Area Number 17K08620
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General medical chemistry
Research InstitutionKitasato University (2019)
University of Tsukuba (2017-2018)

Principal Investigator

Saito Shoko  北里大学, 薬学部, 助教 (70344885)

Co-Investigator(Kenkyū-buntansha) 奥脇 暢  北里大学, 薬学部, 教授 (50322699)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords核膜孔 / 核-細胞質間物質輸送 / 核外輸送 / nucleoporin / 白血病 / 転写 / 核膜孔タンパク質 / エピジェネティック / ヒストン修飾 / がん化 / リボソーム / 癌 / 発現制御 / 細胞・組織
Outline of Final Research Achievements

Nuclear pore complexes are comprised of about 30 different proteins, known as nucleoporins (Nups). Several nup mutations have been found in cancer. However, the molecular mechanisms of these proteins in oncogenesis remain unclear. This study aimed to clarify molecular functions of Nup fusion proteins. We found that Nup fusion proteins have effects on subcellular localization of some Nups and nuclear transport receptors. In addition, SET-Nup214, one of nup fusion proteins, interacts with a histone methyltransferase and affects transcription activity.

Academic Significance and Societal Importance of the Research Achievements

本研究では、予後の悪い、あるいは治療薬に抵抗性との報告がある白血病症例で見られるがん遺伝子産物の機能解析を行った。他のタンパク質との相互作用を明らかにしながら新たな分子機構を解明した点が、学術的に意義がある。そして、がん遺伝子産物の相互作用機構を分子レベルで明らかとすることは、核膜孔タンパク質の質的異常によって引き起こされるがん化の治療法開発の基礎となることを期待している。この点が、本研究成果の社会的意義である。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (8 results)

All 2020 2019 2018 2017 2016

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

  • [Journal Article] Formation of adenovirus DNA replication compartments and viral DNA accumulation sites by host chromatin regulatory proteins including NPM1.2020

    • Author(s)
      Michelle Jane Genoveso, Miharu Hisaoka, Tetsuro Komatsu, Harald Wodrich, Kyosuke Nagata, Mitsuru Okuwaki
    • Journal Title

      FEBS J

      Volume: 287 Issue: 1 Pages: 205-217

    • DOI

      10.1111/febs.15027

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Selective regulation of type II interferon-inducible genes by NPM1/nucleophosmin2018

    • Author(s)
      Abe Mayumi、Lin Jianhuang、Nagata Kyosuke、Okuwaki Mitsuru
    • Journal Title

      FEBS Letters

      Volume: 592 Issue: 2 Pages: 244-255

    • DOI

      10.1002/1873-3468.12952

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Function of Nup98 subtypes and their fusion proteins, Nup98-TopIIβ and Nup98-SETBP1 in nuclear-cytoplasmic transport2017

    • Author(s)
      Saito Shoko、Yokokawa Takafumi、Iizuka Gemmei、Cigdem Sadik、Okuwaki Mitsuru、Nagata Kyosuke
    • Journal Title

      Biochem. Biophs. Res. Commun.

      Volume: 487 Issue: 1 Pages: 96-102

    • DOI

      10.1016/j.bbrc.2017.04.024

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Internal Associations of the Acidic Region of Upstream Binding Factor Control Its Nucleolar Localization2017

    • Author(s)
      Ueshima Shuhei, Nagata Kyosuke, Okuwaki Mitsuru
    • Journal Title

      Mol. Cell Biol.

      Volume: 37 Issue: 22

    • DOI

      10.1128/mcb.00218-17

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Efficient DNA binding of NF-κB requires the chaperone-like function of NPM1.2016

    • Author(s)
      Lin J, Kato M, Nagata K, Okuwaki M.
    • Journal Title

      Nucleic Acids Research

      Volume: gkw1285 Pages: 3707-3723

    • DOI

      10.1093/nar/gkw1285

    • NAID

      120007129193

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Leukemia-associated Nup98 fusion proteins impair nucleocytoplasmic transport through changing the localization of Nup98.2019

    • Author(s)
      Nguyen Thi Thanh Nhan, Kyosuke Nagata, Shoko Saito
    • Organizer
      the 44th FEBS Congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Leukemia-associated Nup98 fusion proteins have the same effect as Nup98 knockdown on nucleocytoplasmic transport.2019

    • Author(s)
      Nguyen Thi Thanh Nhan, Kyosuke Nagata, Shoko Saito
    • Organizer
      The 1st University of Tsukuba-University of Science Joint Young Researcher Meeting in Biomedical Science
    • Related Report
      2018 Research-status Report
  • [Presentation] 核小体の構造と機能におけるNPM1の役割2018

    • Author(s)
      奥脇暢
    • Organizer
      第5回リボソームミーティング
    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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