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The role of ER-resident transmembrane protein OASIS in cellular senescence

Research Project

Project/Area Number 17K15599
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General medical chemistry
Research InstitutionHiroshima University

Principal Investigator

Asada Rie  広島大学, 医系科学研究科(医), 助教 (70751882)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords細胞老化 / 小胞体 / DNA損傷 / 核膜
Outline of Final Research Achievements

In this study, we showed a role of ER-resident transcription factor OASIS in cellular senescence. The expression and activation of OASIS are induced by DNA damage in murine primary astrocyte. Investigation of OASIS KO astrocyte revealed that cell cycle arrest and the transition to cellular senescence after DNA damage are repressed compared to WT. Additionally, the expression of a series of senescence-associated secretory phenotype (SASP) related genes is decreased in KO. Collectively, DNA damage induces OASIS expression and activation, and OASIS promotes cellular senescence thorough transcription of cell cycle and SASP related genes.

Academic Significance and Societal Importance of the Research Achievements

細胞老化とは、DNA損傷などによってゲノム不安定性を持った細胞が増殖するのを防ぐための癌抑制機構である。本研究課題により、OASISが細胞老化を促進する役割がある事が明らかとなった。過去の解析から、複数種の癌細胞においてOASISの発現が低下していることが明らかとなっている。今後、細胞老化におけるOASISの機能をさらに詳細に解析するともに、癌化との関連性を明らかにしていく事で、新たな視点からの癌治療法開発へと繋がる可能性が期待される。

Report

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

    (12 results)

All 2019 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (6 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] NFAT5 up-regulates expression of the kidney-specific ubiquitin ligase gene Rnf183 under hypertonic conditions in inner-medullary collecting duct cells.2019

    • Author(s)
      Maeoka Y, Wu Y, Okamoto T, Kanemoto S, Guo XP, Saito A, Asada R, Matsuhisa K, Masaki T, Imaizumi K, Kaneko M.
    • Journal Title

      J Biol Chem.

      Volume: 294 Issue: 1 Pages: 101-115

    • DOI

      10.1074/jbc.ra118.002896

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Shutdown of ER-associated degradation pathway rescues functions of mutant iduronate 2-sulfatase linked to mucopolysaccharidosis type II.2018

    • Author(s)
      Osaki Y, Saito A, Kanemoto S, Kaneko M, Matsuhisa K, Asada R, Masaki T, Orii K, Fukao T, Tomatsu S, Imaizumi K
    • Journal Title

      Cell Death Dis.

      Volume: 9 Issue: 8 Pages: 808-808

    • DOI

      10.1038/s41419-018-0871-8

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Axonal Activation of the Unfolded Protein Response Promotes Axonal Regeneration Following Peripheral Nerve Injury.2018

    • Author(s)
      Ohtake Y, Matsuhisa K, Kaneko M, Kanemoto S, Asada R, Imaizumi K, Saito A.
    • Journal Title

      Neuroscience

      Volume: 375 Pages: 34-48

    • DOI

      10.1016/j.neuroscience.2018.02.003

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sec16A, a key protein in COPII vesicle formation, regulates the stability and localization of the novel ubiquitin ligase RNF183.2018

    • Author(s)
      Wu Y, Guo XP, Kanemoto S, Maeoka Y, Saito A, Asada R, Matsuhisa K, Ohtake Y, Imaizumi K, Kaneko M.
    • Journal Title

      PLoS One

      Volume: 13 Issue: 1 Pages: e0190407-e0190407

    • DOI

      10.1371/journal.pone.0190407

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuronal activity-dependent local activation of dendritic unfolded protein response promotes expression of brain-derived neurotrophic factor in cell soma.2018

    • Author(s)
      Saito A, Cai L, Matsuhisa K, Ohtake Y, Kaneko M, Kanemoto S, Asada R, Imaizumi K.
    • Journal Title

      Journal of Neurochemistry

      Volume: 144 Issue: 1 Pages: 35-49

    • DOI

      10.1111/jnc.14221

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ER Stress and Disease: Toward Prevention and Treatment2017

    • Author(s)
      Kaneko M, Imaizumi K, Saito A, Kanemoto S, Asada R, Matsuhisa K, Ohtake Y.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 40 Issue: 9 Pages: 1337-1343

    • DOI

      10.1248/bpb.b17-00342

    • NAID

      130006038767

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] アストロサイトの核膜ストレスを制御する小胞体膜タンパク質2019

    • Author(s)
      松久幸司、金子雅幸、齋藤敦、浅田梨絵、今泉和則
    • Organizer
      『広島神経医科学研究会』第3回学生・若手研究者のポスター発表会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 小胞体局在膜貫通型転写因子OASISの核ブレブ集積機構2019

    • Author(s)
      松久幸司、浅田梨絵、金子雅幸、今泉和則
    • Organizer
      新学術領域「オルガネラ・ゾーン」第1回若手の会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ER-resident transmembrane transcription factor OASIS accumulates in the nuclear bleb in response to the disruption of the nuclear lamina2018

    • Author(s)
      Matsuhisa K, Asada R, Kaneko M, Imaizumi K.
    • Organizer
      ASCB | EMBO 2018 Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 小胞体ストレストランスデューサーOASISの核膜blebにおける特徴的な局在と機能について2018

    • Author(s)
      松久幸司、浅田梨絵、金子雅幸、今泉和則
    • Organizer
      第19回ORIGIN神経科学研究会2018
    • Related Report
      2018 Annual Research Report
  • [Presentation] DNA品質管理を担う核-小胞体連携ゾーンの解析2018

    • Author(s)
      今泉和則、松久幸司、浅田梨絵、金子雅幸
    • Organizer
      第1回新学術領域「オルガネラ・ゾーン」全体班会議
    • Related Report
      2018 Annual Research Report
  • [Presentation] 小胞体膜タンパク質OASISの核膜への局所的集積とその生理的意義2017

    • Author(s)
      浅田梨絵、金子雅幸、今泉和則
    • Organizer
      生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2020-03-30  

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