The anaphase-promoting complex/cyclosome (APC/C) is a multi-subunit, multifunctional ubiquitin ligase that controls the temporal degradation of numerous cell cycle regulatory proteins to direct the unidirectional cell cycle phases. Several different mechanisms contribute to ensure the correct order of substrate modification by the APC/C complex. Recent advances in biochemical, biophysical and structural studies of APC/C have provided a deep mechanistic insight into the working of this complex ubiquitin ligase. This complex displays remarkable conformational flexibility in response to various binding partners and post-translational modifications, which together regulate substrate selection and catalysis of APC/C. Apart from this, various features and modifications of the substrates also influence their recognition and affinity to APC/C complex. Ultimately, temporal degradation of substrates depends on the kind of ubiquitin modification received, the processivity of APC/C, and other extrinsic mechanisms. This review discusses our current understanding of various intrinsic and extrinsic mechanisms responsible for ‘substrate ordering’ by the APC/C complex.

中文翻译：

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后期促进复合物/环体对底物泛素化的时间调节机制


后期促进复合物/环体 (APC/C) 是一种多亚基、多功能泛素连接酶，可控制众多细胞周期调节蛋白的暂时降解，以指导单向细胞周期阶段。几种不同的机制有助于确保 APC/C 复合物修饰底物的正确顺序。 APC/C 的生物化学、生物物理和结构研究的最新进展为这种复杂的泛素连接酶的工作提供了深入的机制见解。该复合物在响应各种结合配偶体和翻译后修饰时表现出显着的构象灵活性，它们共同调节 APC/C 的底物选择和催化。除此之外，底物的各种特征和修饰也会影响它们对 APC/C 复合物的识别和亲和力。最终，底物的时间降解取决于所接受的泛素修饰的类型、APC/C 的持续合成能力和其他外在机制。这篇综述讨论了我们目前对 APC/C 复合体负责“底物排序”的各种内在和外在机制的理解。