SCF-mediated Cdh1 degradation defines a negative feedback system that coordinates cell-cycle progression.
SCF-mediated Cdh1 degradation defines a negative feedback system that coordinates cell-cycle progression.
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DOI：
10.1016/j.celrep.2013.07.031
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发表时间：
2013-08-29
期刊：
影响因子：
8.8
通讯作者：
Wei W
中科院分区：
文献类型：
--
作者：
Fukushima H;Ogura K;Wan L;Lu Y;Li V;Gao D;Liu P;Lau AW;Wu T;Kirschner MW;Inuzuka H;Wei W
适当的细胞周期转变是由后期促进复合体(APC)和Skp1-Cullin1-F-box(SCF)E3泛素连接酶复合体对关键调控因子泛素依赖的降解波驱动的。但APC和SCF活动如何协调以调节细胞周期进程仍很不清楚。我们之前已经证明，APC/CDH1专门将SCF组件Skp2用于降解。在这里，我们继续报道，干细胞因子β-TrCP通过调控CDH1泛素化和随后的降解来相互控制APC/CDH1的活性。此外，我们将Cyclin A和Plk1这两种众所周知的cdh1底物定义为上游修饰酶，它们促进cdh1磷酸化触发cdh1泛素化，并随后通过SCFβ-trcp降解。因此，我们的工作揭示了SCF控制APC的负抑制机制，从而说明了这两个E3连接酶复合体之间的优雅的双重抑制系统，从而创建了APC和SCF活性的有序级联，控制着细胞周期的及时转变。
Proper cell-cycle transitions are driven by waves of ubiquitin-dependent degradation of key regulators by the anaphase-promoting complex (APC) and Skp1-Cullin1-F-box (SCF) E3 ubiquitin ligase complexes. But precisely how APC and SCF activities are coordinated to regulate cell-cycle progression remains largely unclear. We previously showed that APC/Cdh1 earmarks the SCF component Skp2 for degradation. Here, we continue to report that SCFβ-TRCP reciprocally controls APC/Cdh1 activity by governing Cdh1 ubiquitination and subsequent degradation. Furthermore, we define both cyclin A and Plk1, two well-known Cdh1 substrates, as upstream modifying enzymes that promote Cdh1 phosphorylation to trigger Cdh1 ubiquitination and subsequent degradation by SCFβ-TRCP. Thus, our work reveals a negative repression mechanism for SCF to control APC, thereby illustrating an elegant dual repression system between these two E3 ligase complexes to create the ordered cascade of APC and SCF activities governing timely cell-cycle transitions.
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