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首页> 外文期刊>Cell cycle >APC/C-mediated degradation in early mitosis: how to avoid spindle assembly checkpoint inhibition.
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APC/C-mediated degradation in early mitosis: how to avoid spindle assembly checkpoint inhibition.

机译：APC / C介导的早期有丝分裂降解：如何避免纺锤体装配检查点受到抑制。

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摘要

The APC/C is an E3 ubiquitin ligase that, by targeting substrates for proteasomal degradation, plays a major role in cell cycle control. In complex with one of two WD40 activator proteins, Cdc20 or Cdh1, the APC/C is active from early mitosis through to late G1 and during this time targets many critical regulators of the cell cycle for degradation. However, this destruction is carefully ordered to ensure that cell cycle events are executed in a timely fashion. Recent studies have begun to shed light on how the APC/C selects different substrates at different times in the cell cycle. One particular problem is how the APC/C recognizes its first set of substrates, Nek2A and cyclin A, in early mitosis when, at this time, the spindle assembly checkpoint (SAC) inhibits most APC/C-dependent degradation. The answer may lie in how substrates are recruited to the APC/C. While checkpoint-dependent substrates appear to require Cdc20 for recruitment, experiments on the early mitotic substrate Nek2A demonstrate that it can bind the APC/C in the absence of Cdc20. The direct interaction of substrates with core subunits of the APC/C could allow their degradation to proceed unhindered even when the SAC is active.
机译：APC / C是一种E3泛素连接酶，通过靶向底物进行蛋白酶体降解，在细胞周期控制中起主要作用。与两种WD40激活蛋白Cdc20或Cdh1中的一种复合时，APC / C从有丝分裂早期到G1晚期均具有活性，在此期间，APC / C的目标是降解细胞周期的许多关键调控因子。但是，仔细销毁此破坏，以确保及时执行细胞周期事件。最近的研究开始阐明APC / C如何在细胞周期的不同时间选择不同的底物。一个特殊的问题是，当此时主轴组件检查点（SAC）抑制大多数APC / C依赖的降解时，APC / C如何在有丝分裂的早期识别其第一组底物Nek2A和细胞周期蛋白A。答案可能在于如何将底物招募到APC / C。尽管依赖检查点的底物似乎需要Cdc20才能募集，但对早期有丝分裂底物Nek2A的实验表明，在不存在Cdc20的情况下，它可以结合APC / C。底物与APC / C核心亚基的直接相互作用即使在SAC处于活动状态时也可以不受阻碍地进行降解。

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