Functional analysis of separase and its novel substrate in the licensing of centrosome duplication

• Project/Area Number: 23590087
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Teikyo Heisei University
• Principal Investigator: TAKAHASHI Mikiko 帝京平成大学, 薬学部, 教授 (90324938)
• Co-Investigator(Kenkyū-buntansha): TADA Shusuke 帝京平成大学, 薬学部, 教授 (00216970) ; MUKAI Hideyuki 神戸大学, バイオシグナル研究センター, 准教授 (80252758) ; MATSUO Kazuhiko 帝京平成大学, 薬学部, 助教 (70599753)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 中心体 / 細胞周期 / 中心体複製 / 分裂期 / セパレース / 複製ライセンシング

Research Abstract

Centrosome assembles the bipolar spindle during mitosis to ensure the equal segregation of replicated chromosomes. It is thereby assumed that the licensing mechanism tightly regulates the initiation of centrosome duplication only once per cell cycle, though precise process remains largely unknown. Separase, a cysteine protease that triggers sister chromatid separation, is known to be involved in this licensing, however, its centrosomal substrate remains unidentified. In this study, we found that the centrosomal protein kendrin is cleaved by separase at a consensus site. Moreover, expression of a non-cleavable kendrin mutant suppresses the initiation of centrosome duplication. Our finding provides the first evidence that kendrin is a novel and crucial substrate for separase at the centrosome involved in the licensing of centrosome duplication.

Research Products

• [Journal Article] More isn’t always better: Limiting centrosome size in interphase. (News & Views) (2013)
  • Author(s): ① Mikiko Takahashi and Kazuhiko Matsuo
  • Journal Title: Cell Cycle Volume: １２ Issue: 6 Pages: 1482-1482
  • DOI: 10.4161/cc.23879
• [Journal Article] Kendrin is a novel substrate for separate involved in the licensing of centriole duplication. (2012)
  • Author(s): Matsuo, K., Ohsumi, K., Iwabuchi, M., Kawamata, T., Ono, Y., Takahashi, M.
  • Journal Title: Curr. Biol. Volume: 22 Issue: 10 Pages: 915-921
  • DOI: 10.1016/j.cub.2012.03.048
  • Peer Reviewed
• [Presentation] Functional analysis of centrosomal protein kendrin in centriole duplication (2013)
  • Author(s): 松尾和彦
  • Organizer: 第86回生化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2013-09-11
• [Presentation] Functional analysis of centrosomal protein kendrin in centriole duplication. (2013)
  • Author(s): 松尾和彦・高橋美樹子
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜
• [Presentation] Possible role of a novel substrate for separase in the licensing of centriole duplication (2011)
  • Author(s): 高橋美樹子
  • Organizer: 第34回分子生物学会年会シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-16
• [Presentation] 中心体複製制御機構におけるseparaseの新規基質候補蛋白質の解析 (2011)
  • Author(s): 松尾和彦
  • Organizer: 第34回分子生物学会年会シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-16
• [Presentation] Possible role of a novel substrate for separase in the licensing of centriole duplication
  • Author(s): Matsuo, K. and Ono, Y., ○Takahashi, M.
  • Organizer: 第34回分子生物学会年会シンポジウム(招待講演)
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] 中心体複製制御機構におけるseparaseの新規基質候補蛋白質の解析
  • Author(s): ○松尾和彦、小野功貴、高橋美樹子
  • Organizer: 第34回分子生物学会年会ポスター
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Remarks]
  • URL: http://pharm.thu.ac.jp/research/unit/bunshisaibou.html
• [Remarks] 帝京平成大学薬学部・薬学研究科
  • URL: http://pharm.thu.ac.jp/research/index.html