Ubiquitination of Cdc20 by the APC Occurs through an Intramolecular Mechanism
Ubiquitination of Cdc20 by the APC Occurs through an Intramolecular Mechanism
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DOI：
10.1016/j.cub.2011.09.051
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发表时间：
2011-11-22
期刊：
影响因子：
9.2
通讯作者：
Toczyski, David P.
中科院分区：
文献类型：
--
作者：
Foe, Ian T.;Foster, Scott A.;Toczyski, David P.
背景资料：细胞通过调节Cdc20和Cdh 1（后期促进复合物（APC）的两种有丝分裂激活剂）来控制晚期有丝分裂的进程。Cdc20蛋白水平在细胞周期的控制是不是很好理解。结果：在这里，我们证明，Cdc20是由多个APC依赖的机制，在芽殖酵母降解。我们发现，大多数Cdc20营业额不涉及第二个激活剂分子，而是依赖于顺式Cdc20 autoubiquitination，而它是结合到其激活剂结合位点的APC核心。与Cdc20底物的反式泛素化不同，APC泛素化Cdc20不依赖于Cdc20的C盒激活APC。Cdc20的周转由这种分子内机制是细胞周期调节，有助于后期后发生的Cdc20水平的下降。有趣的是，在体外高底物水平显着降低Cdc20 autoubiquitination.Conclusion：我们在这里表明，Cdc20波动通过细胞周期通过一个独特的形式APC介导的泛素化。这顺式autoubiquitination可能会优先发生在后期早期，Cdc20底物耗尽后。这表明不同的机制能够在细胞周期的不同时间点靶向Cdc20进行泛素化。
Background: Cells control progression through late mitosis by regulating Cdc20 and Cdh1, the two mitotic activators of the anaphase-promoting complex (APC). The control of Cdc20 protein levels during the cell cycle is not well understood.Results: Here, we demonstrate that Cdc20 is degraded in budding yeast by multiple APC-dependent mechanisms. We find that the majority of Cdc20 turnover does not involve a second activator molecule but instead depends on in cis Cdc20 autoubiquitination while it is bound to its activator-binding site on the APC core. Unlike in trans ubiquitination of Cdc20 substrates, the APC ubiquitinates Cdc20 independent of APC activation by Cdc20's C box. Cdc20 turnover by this intramolecular mechanism is cell cycle regulated, contributing to the decline in Cdc20 levels that occurs after anaphase. Interestingly, high substrate levels in vitro significantly reduce Cdc20 autoubiquitination.Conclusion: We show here that Cdc20 fluctuates through the cell cycle via a distinct form of APC-mediated ubiquitination. This in cis autoubiquitination may preferentially occur in early anaphase, following depletion of Cdc20 substrates. This suggests that distinct mechanisms are able to target Cdc20 for ubiquitination at different points during the cell cycle.