Mechanisms underlying the spatiotemporal activation of separase

2015 Fiscal Year Final Research Report

• Project/Area Number: 24370076
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: Hirota Toru 公益財団法人がん研究会, がん研究所・実験病理部, 部長 (50421368)
• Co-Investigator(Renkei-kenkyūsha): Shindo Norihisa 公益財団法人がん研究会, がん研究所・実験病理部, 研究員 (00512253)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: 細胞分裂 / 染色体分配 / セパレース / 活性プローブ / M期 / 染色体不安定性

Outline of Final Research Achievements

The two key events underlying chromosome segregation are the removal of cohesion between sister chromatids and the subsequent poleward movement of disjoined sisters. How cells coordinate these two processes is not well understood. We aimed to address this question, by setting out a probe for separase activity in living cells. Our probe found that separase undergoes an abrupt activation shortly before anaphase onset, specifically in the vicinity of chromosomes. This activation profile depends on securin, to inhibit separase's protease activity and target it to chromosomes. We surprisingly found that, subsequent to its proteolytic activation, separase then binds to and inhibits a subsert of cyclin B1-Cdk1, which antagonizes Cdk1-mediated phosphorylation on chromosomes and facilitates poleward movement of sisters in anaphase. Therefore, separase coordinates two key processes to achieve simultaneous and abrupt separation of sister chromatids.

Free Research Field

細胞生物学、染色体動態学