The role of CAPN7 in the adaptation to environmental change

• Project/Area Number: 25440059
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Tokyo 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: ¥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.

Research Products

• [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
  • 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
  • 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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Involvement of calpain-7 in epidermal growth factor receptor degradation via the endosomal sorting pathway (2014)
  • 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
  • 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）
• [Remarks] カルパインプロジェクト
  • URL: http://www.igakuken.or.jp/calpain/
• [Remarks] Calpain Project
  • URL: http://www.igakuken.or.jp/calpain/
• [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/