APC/C: current understanding and future perspectives.
APC/C: current understanding and future perspectives.
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DOI：
10.12688/f1000research.18582.1
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发表时间：
2019-01-01
期刊：
影响因子：
--
通讯作者：
Yamano, Hiroyuki
中科院分区：
文献类型：
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作者：
Yamano, Hiroyuki
姐妹染色单体在细胞分裂后期的分离是细胞周期中最重要的不可挽回的事件，这种分离受称为后期促进复合物/细胞周期体（APC/C）的E3泛素连接酶的调节。APC/C和细胞周期蛋白依赖性激酶1（Cdk 1）只是许多重要的细胞周期调节因子中的两个，分别通过泛素化和磷酸化发挥控制作用。APC/C的时间和空间调节是通过多种机制实现的，包括磷酸化、与结构相关的共激活剂Cdc 20和Cdh 1的相互作用、不同E2泛素缀合酶的负载、与抑制剂的结合以及对各种底物的差异亲和力。自25年前发现APC/C以来，深入的研究已经揭示了APC/C调控的许多方面，但我们仍然远远没有充分了解这一重要的细胞机制。最近的高分辨率低温电子显微镜分析和APC/C的重建大大推进了我们对APC/C的酶特性的分子机制的理解。在这篇综述中，我们将研究APC/C法规的历史背景和当前的理解。
The separation of sister chromatids at anaphase, which is regulated by an E3 ubiquitin ligase called the anaphase-promoting complex/cyclosome (APC/C), is arguably the most important irrevocable event during the cell cycle. The APC/C and cyclin-dependent kinase 1 (Cdk1) are just two of the many significant cell cycle regulators and exert control through ubiquitylation and phosphorylation, respectively. The temporal and spatial regulation of the APC/C is achieved by multiple mechanisms, including phosphorylation, interaction with the structurally related co-activators Cdc20 and Cdh1, loading of distinct E2 ubiquitin-conjugating enzymes, binding with inhibitors and differential affinities for various substrates. Since the discovery of APC/C 25 years ago, intensive studies have uncovered many aspects of APC/C regulation, but we are still far from a full understanding of this important cellular machinery. Recent high-resolution cryogenic electron microscopy analysis and reconstitution of the APC/C have greatly advanced our understanding of molecular mechanisms underpinning the enzymatic properties of APC/C. In this review, we will examine the historical background and current understanding of APC/C regulation.