APC/C- and Mad2-mediated degradation of Cdc20 during spindle checkpoint activation
APC/C- and Mad2-mediated degradation of Cdc20 during spindle checkpoint activation
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DOI：
10.4161/cc.8.1.7606
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发表时间：
2009-01-01
期刊：
影响因子：
4.3
通讯作者：
Pagano, Michele
中科院分区：
文献类型：
--
作者：
Ge, Sheng;Skaar, Jeffrey R.;Pagano, Michele
纺锤体组装检查点（SAC）是一个重要的机制，它阻止姐妹染色单体分离，直到从纺锤体极点辐射的微管正确地连接到着丝粒。Cdc 20是后期促进复合物/环体（APC/C）的激活剂，已知是SAC通过结合有丝分裂检查点蛋白（如Mad 2和BubR 1）进行抑制的主要下游靶标。在这里，我们报告说，SAC负调控Cdc 20的稳定性，通过靶向它的蛋白酶体依赖性降解。一旦检查点被纺锤体毒物激活，Cdc 20的主要群体通过APC/C降解，这是一个需要Cdc 20与Mad 2结合的事件。我们认为Cdc 20的降解是确保APC/C-Cdc 20响应SAC而失活的关键控制机制。
The spindle assembly checkpoint (SAC) is an important mechanism that prevents the separation of sister chromatids until the microtubules radiating from the spindle poles are correctly attached to the kinetochores. Cdc20, an activator of the Anaphase Promoting Complex/Cyclosome (APC/C), is known as a major downstream target for inhibition by the SAC through the binding of mitotic checkpoint proteins, such as Mad2 and BubR1. Here, we report that the SAC negatively regulates the stability of Cdc20 by targeting it for proteasome-dependent degradation. Once the checkpoint is activated by spindle poisons, a major population of Cdc20 is degraded via APC/C, an event that requires the binding of Cdc20 to Mad2. We propose that the degradation of Cdc20 represents a critical control mechanism to ensure inactivation of APC/C-Cdc20 in response to the SAC.