The regulation of Cdc20 proteolysis reveals a role for the APC components Cdc23 and Cdc27 during S phase and early mitosis
The regulation of Cdc20 proteolysis reveals a role for the APC components Cdc23 and Cdc27 during S phase and early mitosis
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DOI：
10.1016/s0960-9822(98)70298-2
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发表时间：
1998-06-18
期刊：
影响因子：
9.2
通讯作者：
Amon, A
中科院分区：
文献类型：
--
作者：
Prinz, S;Hwang, ES;Amon, A
背景:在真核细胞中，一种特殊的蛋白质水解机制，其目标是含有破坏盒序列的蛋白质进行降解，并使用一种称为后期促进复合体/环体（APC）的泛素连接酶，在有丝分裂的调节中起着关键作用，APC依赖的蛋白质水解在有丝分裂的中期-后期转变时触发姐妹染色单体的分离，并在有丝分裂结束时破坏有丝分裂周期蛋白。Cdc20和Cdh1/Hct1已被鉴定为出芽酵母apc依赖性蛋白水解的底物特异性调节因子。在这里，我们研究了Cdc20和Cdh1/Hct1的细胞周期调控。结果：CDH1/HCT1 RNA和CDH1/HCT1蛋白的水平在整个细胞周期中是恒定的，而CDC20 RNA和CDC20蛋白仅在S期晚期和有丝分裂时存在，CDC20蛋白在整个细胞周期中是不稳定的。Cdc20的不稳定性依赖于编码APC成分的CDC23和CDC27，在G1期，Cdc20内部的破坏盒介导其不稳定性，但在S期和有丝分裂期间，尽管Cdc20的破坏仍然依赖于CDC23和CDC27，但它不依赖于Cdc20的破坏盒。结论：Cdc20与Cdh1/Hct1的调控存在显著差异。此外，APC激活剂Cdc20本身是APC依赖性蛋白水解机制的底物，APC亚基Cdc23和Cdc27在S期和早期有丝分裂期间Cdc20的降解中发挥作用，而这不是由其破坏盒介导的。(C)现代生物有限公司
Background: in eukaryotic cells, a specialized proteolysis machinery that targets proteins containing destruction-box sequences for degradation and that uses a ubiquitin ligase known as the anaphase-promoting complex/cyclosome (APC) plays a key role in the regulation of mitosis, APC-dependent proteolysis triggers the separation of sister chromatids at the metaphase-anaphase transition and the destruction of mitotic cyclins at the end of mitosis, Recently, two highly conserved WD40-repeat proteins, Cdc20 and Cdh1/Hct1 have been identified as substrate-specific regulators of APC-dependent proteolysis in the budding yeast Saccharomyces cerevisiae. Here, we have investigated the cell cycle regulation of Cdc20 and Cdh1/Hct1.Results: Whereas the levels of CDH1/HCT1 RNA and Cdh1/Hct1 protein are constant throughout the cell cycle, CDC20 RNA and Cdc20 protein are present only during late S phase and mitosis and Cdc20 protein is unstable throughout the entire cell cycle. The instability of Cdc20 depends on CDC23 and CDC27, which encode components of the APC, During the G1 phase, a destruction box within Cdc20 mediates its instability, but during S phase and mitosis, although Cdc20 destruction is still dependent on CDC23 and CDC27, it does not depend on the Cdc20 destruction box,Conclusions: There are remarkable differences in the regulation of Cdc20 and Cdh1/Hct1. Furthermore, the APC activator Cdc20 is itself a substrate of the APC-dependent proteolysis machinery, and the APC subunits Cdc23 and Cdc27 have a role in the degradation of Cdc20 during S phase and early mitosis that is not mediated by its destruction box. (C) Current Biology Ltd.