Regulation of the Bub2/Bfal GAP complex by Cdc5 and cell cycle checkpoints
Regulation of the Bub2/Bfal GAP complex by Cdc5 and cell cycle checkpoints
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DOI：
10.1016/s0092-8674(01)00580-3
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发表时间：
2001-11-30
期刊：
影响因子：
64.5
通讯作者：
Elledge, SJ
中科院分区：
文献类型：
--
作者：
Hu, FH;Wang, YC;Elledge, SJ
在有丝分裂过程中，ras相关的GTP酶（Tem 1）结合GTP并激活信号转导通路，使有丝分裂退出。在大多数细胞周期中，Tem 1功能被GTP酶激活蛋白复合物Bfa 1/Bub 2拮抗。Bfa 1/Bub 2复合物是如何调节的还不清楚。我们发现波罗/Cdc 5激酶在有丝分裂出口网络中Bfa 1/Bub 2的上游起作用。Cdc 5磷酸化Bfa 1并拮抗Bfa 1促进有丝分裂退出的功能。bfa 1受多个细胞周期检查点调控。纺锤体组装和纺锤体方向检查点抑制Bfa 1磷酸化。DNA损伤不会抑制Bfa 1磷酸化，而是导致：Bfa 1的Rad 53和Dun 1依赖性修饰。因此，Bfa 1的调节可能是由多个检查点途径控制以确保有丝分裂停滞的关键步骤。
During mitosis, a ras-related GTPase (Tem1) binds GTP and activates a signal transduction pathway to allow mitotic exit. During most of the cell cycle, Tem1 function is antagonized by a GTPase-activating protein complex, Bfa1/Bub2. How the Bfa1/Bub2 complex is regulated is not well understood. We find that Polo/ Cdc5 kinase acts upstream of Bfa1/Bub2 in the mitotic exit network. Cdc5 phosphorylates Bfa1 and acts to antagonize Bfa1 function to promote mitotic exit. Bfa1 is regulated by multiple cell cycle checkpoints. The spindle assembly and spindle orientation checkpoints inhibit Bfa1 phosphorylation. DNA damage does not inhibit Bfa1 phosphorylation and instead causes: a Rad53- and Dun1-dependent modification of Bfa1. Regulation of Bfa1 may therefore be a key step controlled by multiple checkpoint pathways to ensure a mitotic arrest.