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The role of CAPN7 in the adaptation to environmental change

Research Project

Project/Area Number 25440059
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Functional biochemistry
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

ONO Yasuko  公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 副参事研究員 (20392376)

Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsカルパイン / プロテアーゼ / タンパク質相互作用 / 致死性 / 相互作用検出 / プロテオーム解析 / 細胞内局在 / 進化的保存性 / ノックアウトマウス / タンパク質代謝 / マウス / ノックアウト / 致死
Outline of Final Research Achievements

Calpain is an intracellular calcium-requiring cysteine protease, functioning to modulate substrate structure and activity by limited proteolysis. The human genome contains 15 different calpain genes. Among them, CAPN7 (previously called PalBH or calpain-7) is most evolutionarily conserved. In the organisms such as yeast and fungi, CAPN7 homologue functions as an activator for a critical transcription factor in adaptation to an increase of environmental pH. To extend our knowledge about this diversely conserved calpain species, this study aimed to examine the role of CAPN7 in higher vertebrates using genetically modified mouse and cultured cells.
In mouse, homozygous knock-out of the Capn7 gene in C57/B6J background results in neonatal lethality. The primary cause of this phenotype still remains unclear; however, it was demonstrated that CAPN7 protease activity is required for the rescue of this phenotype. Potential function of Capn7 by its structure was also suggested.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (8 results)

All 2017 2016 2014 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Acknowledgement Compliant: 3 results,  Open Access: 2 results) Presentation (1 results) Remarks (3 results)

  • [Journal Article] Calpain research for drug discovery: challenges and potential.2016

    • Author(s)
      Ono Y, Saido TC, Sorimachi H
    • Journal Title

      Nat Rev Drug Discov

      Volume: 15 Issue: 12 Pages: 854-876

    • DOI

      10.1038/nrd.2016.212

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] An eccentric calpain, CAPN3/p94/calpain-3.2016

    • Author(s)
      Ono, Y., Ojima, K., Shinkai-Ouchi, F., Hata, S., and Sorimachi, H.
    • Journal Title

      Biochimie

      Volume: 122 Pages: 169-87

    • DOI

      10.1016/j.biochi.2015.09.010

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Predictions of Cleavability of Calpain Proteolysis by Quantitative Structure-Activity Relationship Analysis Using Newly Determined Cleavage Sites and Catalytic Efficiencies of an Oligopeptide Array.2016

    • Author(s)
      Shinkai-Ouchi F, Koyama S, Ono Y, Hata S, Ojima K, Shindo M, duVerle D, Ueno M, Kitamura F, Doi N, Takigawa I, Mamitsuka H, Sorimachi H.
    • Journal Title

      Mol Cell Proteomics

      Volume: 15 Issue: 4 Pages: 1262-1280

    • DOI

      10.1074/mcp.m115.053413

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Involvement of calpain-7 in epidermal growth factor receptor degradation via the endosomal sorting pathway2014

    • Author(s)
      Yuki Maemoto, Yasuko Ono, Satomi Kiso, Hideki Shibata, Terunao Takahara, Hiroyuki Sorimachi, Masatoshi Maki
    • Journal Title

      The FEBS Journal

      Volume: 281 Issue: 16 Pages: 3642-3655

    • DOI

      10.1111/febs.12886

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] カルパイン3の自己分解と活性化について2017

    • Author(s)
      1.小野弥子,土井奈穂子,反町洋之
    • Organizer
      2017年度日本農芸化学会大会
    • Place of Presentation
      京都女子大学(京都府京都市)
    • Related Report
      2016 Annual Research Report
  • [Remarks] カルパインプロジェクト

    • URL

      http://www.igakuken.or.jp/calpain/

    • Related Report
      2016 Annual Research Report
  • [Remarks] Calpain Project

    • URL

      http://www.igakuken.or.jp/calpain/

    • Related Report
      2015 Research-status Report
  • [Remarks] 公益財団法人東京都医学総合研究所 ホームページ

    • URL

      http://www.igakuken.or.jp/

    • Related Report
      2014 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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