How cyclin A destruction escapes the spindle assembly checkpoint
How cyclin A destruction escapes the spindle assembly checkpoint
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DOI：
10.1083/jcb.201001083
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发表时间：
2010-08-23
影响因子：
7.8
通讯作者：
Pines, Jonathon
中科院分区：
文献类型：
--
作者：
Di Fiore, Barbara;Pines, Jonathon
后期促进复合物/环体（APC/C）是有丝分裂所必需的泛素连接酶，其确保特定蛋白质在特定时间降解以控制有丝分裂事件的顺序。APC/C共激活因子Cdc 20被纺锤体组装检查点（SAC）靶向以限制APC/C活性直到中期，但早期底物（如细胞周期蛋白A）在活性检查点存在下降解。Cdc 20和细胞周期蛋白依赖性激酶辅因子Cks是细胞周期蛋白A破坏所必需的，但它们如何使检查点抗性破坏尚未阐明。在这项研究中，我们回答了这个问题：我们表明，细胞周期蛋白A的N末端直接结合到Cdc 20，并具有足够的亲和力，它可以胜过SAC蛋白。随后，Cks蛋白通过将细胞周期蛋白A-Cdc 20结合到APC/C上，在存在活性检查点的情况下促进细胞周期蛋白A降解是必要的和足够的。
The anaphase-promoting complex/cyclosome (APC/C) is the ubiquitin ligase essential to mitosis, which ensures that specific proteins are degraded at specific times to control the order of mitotic events. The APC/C coactivator, Cdc20, is targeted by the spindle assembly checkpoint (SAC) to restrict APC/C activity until metaphase, yet early substrates, such as cyclin A, are degraded in the presence of the active checkpoint. Cdc20 and the cyclin-dependent kinase cofactor, Cks, are required for cyclin A destruction, but how they enable checkpoint-resistant destruction has not been elucidated. In this study, we answer this problem: we show that the N terminus of cyclin A binds directly to Cdc20 and with sufficient affinity that it can outcompete the SAC proteins. Subsequently, the Cks protein is necessary and sufficient to promote cyclin A degradation in the presence of an active checkpoint by binding cyclin A-Cdc20 to the APC/C.