The mitotic checkpoint complex (MCC): looking back and forth after 15 years.
The mitotic checkpoint complex (MCC): looking back and forth after 15 years.
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DOI：
10.3934/molsci.2016.4.597
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发表时间：
2016
影响因子：
1.4
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Liu ST;Zhang H
有丝分裂检查点是一种特殊的信号转导途径，有助于染色体分离的保真度。检查点的信号来源于有缺陷的动粒-微管相互作用，并导致有丝分裂检查点复合体(MCC)的形成，有丝分裂检查点复合体是后期促进复合体/环体(APC/C)的高效抑制物，后者是E3泛素连接酶，对后期启动至关重要。在过去的15年里，关于MCC及其与APC/C相互作用的许多重要问题得到了广泛的研究和讨论，例如MCC的确切组成，它在细胞周期中是如何组装的，它如何抑制APC/C，以及MCC如何被分解以允许APC/C激活。这些努力已经达到了最近报道的人类MCC的结构模型：近原子分辨率的APC/C超复合体，揭示了有丝分裂检查点机制的多个方面。然而，关于MCC的令人困惑的说法仍然分散在文献中，这使得学生和科学家都很难对MCC的组成、结构、功能和动力学有一个清晰的了解。本文将梳理关于MCC的一些最流行的概念或误解，讨论我们目前的理解，提出一个关于CDC20泛素化调控的综合模型，并为MCC的下一阶段研究提出一些未来的努力和注意事项。
The mitotic checkpoint is a specialized signal transduction pathway that contributes to the fidelity of chromosome segregation. The signaling of the checkpoint originates from defective kinetochore-microtubule interactions and leads to formation of the mitotic checkpoint complex (MCC), a highly potent inhibitor of the Anaphase Promoting Complex/Cyclosome (APC/C)—the E3 ubiquitin ligase essential for anaphase onset. Many important questions concerning the MCC and its interaction with APC/C have been intensively investigated and debated in the past 15 years, such as the exact composition of the MCC, how it is assembled during a cell cycle, how it inhibits APC/C, and how the MCC is disassembled to allow APC/C activation. These efforts have culminated in recently reported structure models for human MCC:APC/C supra-complexes at near-atomic resolution that shed light on multiple aspects of the mitotic checkpoint mechanisms. However, confusing statements regarding the MCC are still scattered in the literature, making it difficult for students and scientists alike to obtain a clear picture of MCC composition, structure, function and dynamics. This review will comb through some of the most popular concepts or misconceptions about the MCC, discuss our current understandings, present a synthesized model on regulation of CDC20 ubiquitination, and suggest a few future endeavors and cautions for next phase of MCC research.