MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Curr Opin Struct Biol. 2014 Dec;29:1-9. doi: 10.1016/j.sbi.2014.08.003. Epub 2014 Aug 24.
The anaphase-promoting complex/cyclosome (APC/C) is a large multimeric complex that functions as a RING domain E3 ubiquitin ligase to regulate ordered transitions through the cell cycle. It does so by controlling the ubiquitin-mediated proteolysis of cell cycle proteins, notably cyclins and securins, whose degradation triggers sister chromatid disjunction and mitotic exit. Regulation of APC/C activity and modulation of its substrate specificity are subject to intricate cell cycle checkpoints and control mechanisms involving the switching of substrate-specifying cofactors, association of regulatory protein complexes and post-translational modifications. This review discusses the recent progress towards understanding the overall architecture of the APC/C, the molecular basis for degron recognition and ubiquitin chain synthesis, and how these activities are regulated.
后期促进复合物/环体（APC/C）是一个大型的多聚体复合物，作为一个 RING 结构域 E3 泛素连接酶，通过调控细胞周期中的有序转变发挥作用。它通过控制细胞周期蛋白和 securin 等细胞周期蛋白的泛素介导的蛋白水解来实现这一点，这些蛋白的降解触发姐妹染色单体分离和有丝分裂退出。APC/C 活性的调节和其底物特异性的调节受到复杂的细胞周期检查点和控制机制的影响，这些机制涉及到底物特异性辅助因子的切换、调节蛋白复合物的结合和翻译后修饰。这篇综述讨论了在理解 APC/C 的整体结构、degron 识别和泛素链合成的分子基础以及这些活性如何被调节方面的最新进展。
