Mechanisms underlying the spatiotemporal activation of separase
| Project/Area Number |
24370076
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Molecular biology
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| Research Institution | Japanese Foundation for Cancer Research |
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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)
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| 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)
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| Project Period (FY) |
2012-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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| 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 / プロテアーゼ / 分子間相互作用 / ライブイメージング / 染色体構築 / 活性化機構 / シグナル伝達 / がん / サイクリン依存性キナーゼ / セキュリン / 染色体の分離 / 中期後期移行 |
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| 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.
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Report
(5 results)
Research Products
(49 results)
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[Journal Article] Esco1 Acetylates Cohesin via a Mechanism Different from That of Esco22015
Author(s)
Masashi Minamino, Mai Ishibashi, Ryuichiro Nakato, Kazuhiro Akiyama, Hiroshi Tanaka, Yuki Kato, Lumi Negishi, Toru Hirota, Takashi Sutani, Masashige Bando, Katsuhiko Shirahige
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Journal Title
Curr Biol
Volume: 25
Pages: 1694-1706
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] がんと染色体2015
Author(s)
広田 亨
Organizer
第69回日本臨床細胞学会細胞検査士教育セミナー
Place of Presentation
東京
Year and Date
2015-08-30
Related Report
Invited
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