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Nuclear export mechanism of misfolded proteins

Research Project

Project/Area Number 16K20998
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Cell biology
Functional biochemistry
Research InstitutionThe University of Tokyo

Principal Investigator

Hirayama Shoshiro  東京大学, 大学院薬学系研究科(薬学部), 助教 (80548280)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsユビキチン / プロテアソーム / タンパク質品質管理 / 細胞内輸送 / タンパク質凝集体 / 神経変性疾患 / タンパク質凝集 / 細胞生物学 / 蛋白質品質管理
Outline of Final Research Achievements

In mammalian cells, it is known that the misfolded or the ubiquitinated proteins are sequestered into specific deposition sites in the cytoplasm not in the nucleus such as aggresome and ALIS. Formation of these cytoplasmic aggregates is considered to be cytoprotective. However, it is unknown why aggresome and ALIS form in the cytosol but not in the nucleus.
In this study, we found that the ubiquitinated proteins were exported from the nucleus and cytosol. Furthermore, we also showed that ubiquitin binding protein UBIN and its cofactor POST cooperatively export the ubiquitinated proteins in an exportin dependent manner.

Report

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

    (11 results)

All 2018 2017 2016

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (7 results) (of which Int'l Joint Research: 6 results)

  • [Journal Article] Nuclear export of ubiquitinated proteins via the UBIN-POST system2018

    • Author(s)
      S. Hirayama, M. Sugihara, D. Morito, S. Iemura, T. Natsume, K. Nagata
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: in press Issue: 18

    • DOI

      10.1073/pnas.1711017115

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A small-molecule compound inhibits a collagen-specific molecular chaperone and could represent a potential remedy for fibrosis2017

    • Author(s)
      S. Ito, K. Ogawa, K. Takeuchi, M. Takagi, M. Yoshida, T. Hirokawa, S. Hirayama, K. Shin-Ya, I. Shimada, T. Doi, N. Goshima, T. Natsume, K. Nagata
    • Journal Title

      J. Biol. Chem.

      Volume: 292 Issue: 49 Pages: 20076-20085

    • DOI

      10.1074/jbc.m117.815936

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ubiquitin-Binding Protein CG5445 Suppresses Aggregation and Cytotoxicity of Amyotrophic Lateral Sclerosis-linked TDP-43 in Drosophila.2017

    • Author(s)
      Uechi H, Kuranaga E, Iriki T, Takano K, Hirayama S, Miura M, Hamazaki J, Murata S.
    • Journal Title

      Molecular and Cellular Biology

      Volume: 3 Issue: 3

    • DOI

      10.1128/mcb.00195-17

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The aspartyl protease DDI2 activates Nrf1 to compensate for proteasome dysfunction.2016

    • Author(s)
      Koizumi S, Irie T, Hirayama S, Sakurai Y, Yashiroda H, Naguro I, Ichijo H, Hamazaki J, Murata S.
    • Journal Title

      Elife

      Volume: 18357 Pages: 18357-18357

    • DOI

      10.7554/elife.18357

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] A comprehensive analysis of modulators regulating tau aggregation2017

    • Author(s)
      Shoshiro Hirayama, Yasuyuki Sakurai, Kazuki Murata, Shigeo Murata
    • Organizer
      EMBO Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ユビキチン化を介した構造異常タンパク質の核外排出機構の解析2017

    • Author(s)
      平山尚志郎、大東宣貴、八代田英樹、村田茂穂
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The mechanism of cellular senescence induced by proteasome dysfunction2017

    • Author(s)
      Tomohiro Iriki, Eiichi Hasimoto, Shoshiro Hirayama, Jun Hamazaki, Shigeo Murata
    • Organizer
      Stockholm-Tokyo University Partnership, Living longer and healthier in an ageing world
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] HECT型ユビキチンリガーゼHul5は変異型SOD1の核外排出に関与する2017

    • Author(s)
      大東宣貴、平山尚志郎、八代田英樹、村田茂穂
    • Organizer
      酵母遺伝学フォーラム
    • Related Report
      2017 Annual Research Report
  • [Presentation] HECTドメインE3ユビキチンリガーゼHUL5は変性タンパク質の核外排出に関与する2016

    • Author(s)
      大東宣貴、平山尚志郎、八代田英樹、村田茂穂
    • Organizer
      第39回 日本分子生物学会年会
    • Place of Presentation
      横浜国際平和会議場 (神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 核および細胞質特異的ユビキチン依存性タンパク質分解制御機構の解析2016

    • Author(s)
      横森一泉、櫻井靖之、平山尚志郎、村田茂穂
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜国際平和会議場 (神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] A Genome-wide siRNA Screen for Modulators of Tau Aggregation2016

    • Author(s)
      Yasuyuki Sakurai, Shoshiro Hirayama, Shigeo Murata
    • Organizer
      FASEB - Ubiquitin & Cellular Regulation
    • Place of Presentation
      Bozeman (U.S.A.)
    • Year and Date
      2016-06-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2019-03-29  

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