Mad2 and the APC/C compete for the same site on Cdc20 to ensure proper chromosome segregation.
Mad2 and the APC/C compete for the same site on Cdc20 to ensure proper chromosome segregation.
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Mad2 和 APC/C 竞争 Cdc20 上的同一位点，以确保正确的染色体分离。
DOI：
10.1083/jcb.201205170
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发表时间：
2012-10-01
期刊：
影响因子：
--
通讯作者：
Pines J
中科院分区：
文献类型：
--
作者：
Izawa D;Pines J
同时，BubR1作为纺锤体组装检查点复合体中的假底物抑制CDc20，MAD2与CDc20结合，防止APC/C的激活和随后的有丝分裂退出，当染色体附着未完成时。纺锤体组装检查点(SAC)是确保适当的染色体分离从而维持基因组稳定性所必需的。SAC监测染色体附着，任何未附着的染色体都会产生一个“等待后期”信号，阻止染色体分离。SAC的靶标是CDC20，它激活后期促进复合体/环体(APC/C)，通过泛素化Securin和Cyclin B1来触发后期和有丝分裂退出。由SAC形成的抑制复合体最近被证明通过作为假底物抑制剂来抑制CDC20，但在本文中，我们证明了MAD2也通过直接与APC/C结合所需的位点来抑制CDC20。MAD2和APC/C在体外竞争CDC20，而一个不稳定与MAD2结合的CDC20突变体在体内取消了SAC。因此，我们提供了对CDC20如何绑定APC/C的见解，并揭示了SAC抑制APC/C的第二种机制。
At the same time that BubR1 acts as a pseudosubstrate inhibitor in the spindle assembly checkpoint complex to inhibit Cdc20, Mad2 binds to Cdc20 to prevent activation of APC/C and subsequent mitotic exit when chromosome attachment is not complete. The spindle assembly checkpoint (SAC) is essential to ensure proper chromosome segregation and thereby maintain genomic stability. The SAC monitors chromosome attachment, and any unattached chromosomes generate a “wait anaphase” signal that blocks chromosome segregation. The target of the SAC is Cdc20, which activates the anaphase-promoting complex/cyclosome (APC/C) that triggers anaphase and mitotic exit by ubiquitylating securin and cyclin B1. The inhibitory complex formed by the SAC has recently been shown to inhibit Cdc20 by acting as a pseudosubstrate inhibitor, but in this paper, we show that Mad2 also inhibits Cdc20 by binding directly to a site required to bind the APC/C. Mad2 and the APC/C competed for Cdc20 in vitro, and a Cdc20 mutant that does not bind stably to Mad2 abrogated the SAC in vivo. Thus, we provide insights into how Cdc20 binds the APC/C and uncover a second mechanism by which the SAC inhibits the APC/C.
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