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Analysis of function of Hikeshi affecting cellular homeostasis

Research Project

Project/Area Number 18H02442
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 44010:Cell biology-related
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Imamoto Naoko  国立研究開発法人理化学研究所, 開拓研究本部, 主任研究員 (20202145)

Co-Investigator(Kenkyū-buntansha) 小瀬 真吾  国立研究開発法人理化学研究所, 開拓研究本部, 専任研究員 (90333278)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2018: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Keywords核ー細胞質間輸送 / 分子シャペロンHsp70 / HSF1 / タンパク質毒性ストレス / Hikeshi / タンパク質の恒常性 / 分子シャペロンHsp70 HSF1 / 熱ストレス / プロテオスタシス / 熱ショックタンパク質 / 転写因子HSF1
Outline of Final Research Achievements

The prime feature of eukaryotic cells is the separation of the intracellular space into two compartments, the nucleus and the cytoplasm. Active nuclear transport is crucial for the maintenance of this separation. In this study, we focus on a nuclear transport receptor named Hikeshi, which mediates the heat stress-induced nuclear import of Hsp70s. The cytoplasmic function of Hsp70 is well studied, but its nuclear roles remain obscure. We found Hikeshi regulates the nucleocytoplasmic distribution of Hsp70 not only under heat shock conditions but also under nonstressed conditions. Nuclear Hsp70 affects the transcriptional activity of HSF1 and nuclear proteostasis under nonstressed conditions. Depletion of Hikeshi induces a reduction in nuclear Hsp70 and activate HSF1 under nonstressed conditions, and impair the heat shock response. Thus, proper nucleocytoplasmic distribution of Hsp70, mediated by Hikeshi, is required for nuclear proteostasis and adaptive response to heat shock.

Academic Significance and Societal Importance of the Research Achievements

核-細胞質間輸送という、生体にとって基本的な細胞内反応の生理的重要性の一例を分子のレベルで具体的に明らかにすることができた意義は大きい。Hsp70はタンパク質の折りたたみや凝集阻止を担う分子シャペロンとして細胞質における機能が有名である。このHsp70を核に輸送する運搬体Hikeshiを同定したが、Hsp70の核内機能が不明であった。Hikeshiの解析から、核内Hsp70が、転写因子HSF1の活性を制御することで核内タンパク質の恒常性維持を担うことが明らかになった。その破綻は生体に重篤な作用を示す。核と細胞質という、真核生物の基本となる分子の細胞内局在の重要性が改めて示された。

Report

(4 results)
  • 2021 Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (30 results)

All 2022 2021 2020 2019 2018

All Journal Article (7 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (22 results) (of which Int'l Joint Research: 1 results,  Invited: 7 results) Book (1 results)

  • [Journal Article] Lack of Hikeshi activates HSF1 activity under normal conditions and disturbs the heat shock response2022

    • Author(s)
      Shingo Kose、Kenichiro Imai、 Ai Watanabe、Akira Nakai、Yutaka Suzuki、Naoko Imamoto
    • Journal Title

      Life Science Alliance

      Volume: in press

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Methods to separate nuclear soluble fractions reflecting localizations in living cells2021

    • Author(s)
      Ogawa Yutaka、Imamoto Naoko
    • Journal Title

      iScience

      Volume: 24 Issue: 12 Pages: 103503-103503

    • DOI

      10.1016/j.isci.2021.103503

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stochastic chromatin packing of 3D mitotic chromosomes revealed by coherent X-rays2021

    • Author(s)
      Sung Daeho、Lim Chan、Takagi Masatoshi、Jung Chulho、Lee Heemin、Cho Do Hyung、Shin Jae-Yong、Ahn Kangwoo、Hwang Junha、Nam Daewoong、Kohmura Yoshiki、Ishikawa Tetsuya、Noh Do Young、Imamoto Naoko、Jeon Jae-Hyung、Song Changyong
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 118 Issue: 46

    • DOI

      10.1073/pnas.2109921118

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Distinct mutations in importin-β family nucleocytoplasmic transport receptors transportin-SR and importin-13 affect specific cargo binding2021

    • Author(s)
      Kimura M, Imai K, Morinaka Y, Hosono-Sakuma Y, Horton P, Imamoto N
    • Journal Title

      Sci Rep.

      Volume: 11 Issue: 1 Pages: 15649-15649

    • DOI

      10.1038/s41598-021-94948-1

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The intrinsically disordered N‐terminal region of mouse DNA polymerase alpha mediates its interaction with POT1a/b at telomeres2021

    • Author(s)
      Mizuno Takeshi、Hirabayashi Kei、Miyazawa Sae、Kobayashi Yurika、Shoji Kenta、Kobayashi Masakazu、Hanaoka Fumio、Imamoto Naoko、Torigoe Hidetaka
    • Journal Title

      Genes to Cells

      Volume: 26 Issue: 6 Pages: 360-380

    • DOI

      10.1111/gtc.12845

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nuclear import of IER5 is mediated by a classical bipartite nuclear localization signal and is required for HSF1 full activation2020

    • Author(s)
      Shotaro Yamano, Makoto Kimura, Yu Chen, Naoko Imamoto, Rieko Ohki
    • Journal Title

      Experimental Cell Research

      Volume: 386 Issue: 1 Pages: 111686-111686

    • DOI

      10.1016/j.yexcr.2019.111686

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Editorial overview: Cell nucleus2019

    • Author(s)
      Imamoto Naoko、Larson Daniel
    • Journal Title

      Current Opinion in Cell Biology

      Volume: 58 Pages: iii-iv

    • DOI

      10.1016/j.ceb.2019.06.004

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 核-細胞質間輸送経路の多様性と細胞機能2021

    • Author(s)
      今本尚子
    • Organizer
      生化学会関東支部会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 核-細胞質間輸送の多様性と役割分担2021

    • Author(s)
      今本尚子, 木村誠, 今井賢一郎
    • Organizer
      第73回日本細胞生物学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Analysis of physiological functions of Hikeshi, a nuclear import factor of HSP702021

    • Author(s)
      Shingo Kose, Naoko Imamoto
    • Organizer
      第94回日本生化学会大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Understanding aging through nuclear transport studies2021

    • Author(s)
      Naoko Imamoto
    • Organizer
      RIKEN Aging Project Annual Meeting
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Analysis of Function of Hikeshi2019

    • Author(s)
      Naoko Imamoto
    • Organizer
      NT Nucleocytoplasmic Transport “Airlie” meeting.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Hikeshiが担うHsp70の核内機能の解析2019

    • Author(s)
      今本尚子、小瀬真吾
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Importin α ファミリーによる温度依存的な核-細胞質間輸送制御2019

    • Author(s)
      小川 泰、 今本尚子
    • Organizer
      第19回日本蛋白質科学会年会・第71回日本細胞生物学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 細胞核・細胞質の温度センシング機構の解明2019

    • Author(s)
      今本尚子、小瀬真吾、小川泰
    • Organizer
      新学術領域研究「温度生物学」 2019年 夏の班会議
    • Related Report
      2019 Annual Research Report
  • [Presentation] Hikeshiによる分子シャペロンHSP70核輸送とその機能2019

    • Author(s)
      小瀬真吾
    • Organizer
      第14回日本臨床ストレス応答学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 熱ショックタンパク質Hsp70の核内輸送を担うHikeshiの機能 細胞質の温度センシング機構の解明」2019

    • Author(s)
      今本尚子、小瀬真吾、小川泰
    • Organizer
      新学術領域研究「温度生物学」 2019年 冬の班会議
    • Related Report
      2019 Annual Research Report
  • [Presentation] 今本細胞核機能研究室2019

    • Author(s)
      今本尚子
    • Organizer
      埼玉大学彩の国女性研究者ネットワーク訪問セミナー
    • Related Report
      2019 Annual Research Report
  • [Presentation] 今本細胞核機能研究室2019

    • Author(s)
      今本尚子
    • Organizer
      埼玉県立総合教育センター(埼玉県高校理科教員研修研修)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 核-細胞質間輸送運搬体Hikeshi の機能2019

    • Author(s)
      今本尚子
    • Organizer
      第4回Integrated Lipidology領域会議
    • Related Report
      2018 Annual Research Report
  • [Presentation] 熱ショックタンパク質Hsp70の核内輸送を担う輸送運搬体Hikeshiの機能2018

    • Author(s)
      今本 尚子
    • Organizer
      第91回日本生化学会大会”ストレス応答によるプロテオスタシス制御の新展開”シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 細胞質・温度センシング機構(ImportinとHikehiが担う核-細胞質間輸送)2018

    • Author(s)
      今本 尚子
    • Organizer
      新学術領域研究「温度生物学」平成30年度夏の班会議
    • Related Report
      2018 Annual Research Report
  • [Presentation] 核内輸送運搬体 Hikeshiの機能解析から見えてきた Hsp70 の核内機能2018

    • Author(s)
      今本 尚子
    • Organizer
      大阪大学蛋白質研究所セミナー「細胞核とクロマチン構造が操る高次生命現象」
    • Related Report
      2018 Annual Research Report
  • [Presentation] 核内輸送運搬体 Hikeshi の機能解析から見えてきた Hsp70 の核内機能2018

    • Author(s)
      今本 尚子
    • Organizer
      新学術領域研究「温度生物学」平成30年度冬の班会議
    • Related Report
      2018 Annual Research Report
  • [Presentation] 核-細胞質間運搬体Hikeshiの機能2018

    • Author(s)
      今本 尚子
    • Organizer
      「エピゲノム解析を基盤とするがんと老化関連疾患の治療戦略」 山口大学
    • Related Report
      2018 Annual Research Report
  • [Presentation] 核-細胞質間輸送:多様な輸送経路2018

    • Author(s)
      今本尚子
    • Organizer
      新領域開拓課題「細胞進化」交流会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 分子シャペロンHSP70の核内輸送運搬体Hikeshi:その輸送機構と生理機能について2018

    • Author(s)
      小瀬真吾
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 核-細胞質間輸送の温度依存性2018

    • Author(s)
      小川泰
    • Organizer
      Biothermology Workshop 2018
    • Related Report
      2018 Annual Research Report
  • [Presentation] Nuclear transport system responds in a multistep mechanism depending on temperature rises2018

    • Author(s)
      小川泰
    • Organizer
      第70回細胞生物第51回発生生物合同大会
    • Related Report
      2018 Annual Research Report
  • [Book] Thermal Stress and Nuclear Transport. “Thermal Biology”2022

    • Author(s)
      Shingo Kose, Yutaka Ogawa, Naoko Imamoto.
    • Publisher
      Springer Nature
    • Related Report
      2020 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2023-01-30  

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