The Polo-related kinase Cdc5 activates and is destroyed by the mitotic cyclin destruction machinery in S. cerevisiae
The Polo-related kinase Cdc5 activates and is destroyed by the mitotic cyclin destruction machinery in S. cerevisiae
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DOI：
10.1016/s0960-9822(98)70201-5
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发表时间：
1998-04-23
期刊：
影响因子：
9.2
通讯作者：
Morgan, DO
中科院分区：
文献类型：
--
作者：
Charles, JF;Jespersen, SL;Morgan, DO
背景：有丝分裂后期染色体分离后，依赖泛素的有丝分裂周期蛋白降解导致有丝分裂退出。在这一过程中的一个关键步骤是由一种被称为后期促进复合体(APC)的泛素-蛋白质连接酶催化的，其调控机制尚不清楚。酿酒酵母中的Polo相关蛋白激酶CDC5可能编码APC的一个调节子，因为CDC5u的细胞停滞，其晚期有丝分裂表型与细胞周期蛋白破坏缺陷细胞中观察到的类似。在CDC5-1突变细胞中，我们观察到细胞周期蛋白的破坏缺陷和细胞周期蛋白-泛素连接酶活性的降低。CDC5的过表达导致异步化细胞或停滞于中期的细胞中APC活性增加和有丝分裂周期蛋白破坏，CDCS突变或过表达不影响APC底物Pds1的降解，Pds1通常在中期-低-后期转变时降解。在缺乏APC调控蛋白Hct1和CDc20的情况下，过表达CDC5的细胞中的细胞周期蛋白特异性APC活性降低。在G1期，CDC5本身被APC依赖和Hct1依赖的机制降解。结论：在晚期有丝分裂中，CDC5是细胞周期蛋白特异性APC活性的正调节因子。CDC5在G1期的降解可能提供了一种反馈机制，通过这种机制，APC在下一个细胞周期开始时破坏了它的激活物。(C)现代生物有限公司ISSN 0960-9822。
Background: Following chromosome segregation in anaphase, ubiquitin-dependent degradation of mitotic cyclins contributes to the exit from mitosis. A key step in this process is catalyzed by a ubiquitin-protein ligase known as the anaphase-promoting complex (APC), the regulation of which is poorly understood. The Polo-related protein kinase Cdc5 in Saccharomyces cerevisiae might encode a regulator of the APC, because cdc5 mu rant cells arrest with a late mitotic phenotype similar to that observed in cells with defective cyclin destruction.Results: We investigated the role of Cdc5 in the regulation of mitotic cyclin degradation. In cdc5-1 mutant cells, we observed a defect in the destruction of cyclins and a reduction in the cyclin-ubiquitin ligase activity of the APC. Overexpression of CDC5 resulted in increased APC activity and mitotic cyclin destruction in asynchronous cells or in cells arrested in metaphase, CDCS mutation or overexpression did not affect the degradation of the APC substrate Pds1, which is normally degraded at the metaphase-lo-anaphase transition. Cyclin-specific APC activity in cells overexpressing CDC5 was reduced in the absence of the APC regulatory proteins Hct1 and Cdc20. In G1, Cdc5 itself was degraded by an APC-dependent and Hct1 -dependent mechanism.Conclusions: We conclude that Cdc5 is a positive regulator of cyclin-specific APC activity in late mitosis. Degradation of Cdc5 in G1 might provide a feedback mechanism by which the APC destroys its activator at the onset of the next cell cycle. (C) Current Biology Ltd ISSN 0960-9822.