Department of Molecular Cell Biology, University of California at Berkeley, Berkeley, CA 94720-3202, USA.
J Cell Sci. 2012 Jan 15;125(Pt 2):255-63. doi: 10.1242/jcs.091199.
The covalent modification of proteins with ubiquitin is required for accurate cell division in all eukaryotes. Ubiquitylation depends on an enzymatic cascade, in which E3 enzymes recruit specific substrates for modification. Among ~600 human E3s, the SCF (Skp1-cullin1-F-box) and the APC/C (anaphase-promoting complex/cyclosome) are known for driving the degradation of cell cycle regulators to accomplish irreversible cell cycle transitions. The cell cycle machinery reciprocally regulates the SCF and APC/C through various mechanisms, including the modification of these E3s or the binding of specific inhibitors. Recent studies have provided new insight into the intricate relationship between ubiquitylation and the cell division apparatus as they revealed roles for atypical ubiquitin chains, new mechanisms of substrate and E3 regulation, as well as extensive crosstalk between ubiquitylation enzymes. Here, we review these emerging regulatory mechanisms of ubiquitin-dependent cell cycle control and discuss how their manipulation might provide therapeutic benefits in the future.
泛素化修饰对于所有真核生物中精确的细胞分裂是必需的。泛素化依赖于酶级联反应，其中 E3 酶招募特定的底物进行修饰。在约 600 个人类 E3 中，SCF（Skp1-cullin1-F-box）和 APC/C（有丝分裂促进复合物/细胞周期蛋白体）以驱动细胞周期调节剂的降解而闻名，以完成不可逆的细胞周期转变。细胞周期机制通过各种机制反向调节 SCF 和 APC/C，包括这些 E3 的修饰或特定抑制剂的结合。最近的研究提供了对泛素化和细胞分裂装置之间复杂关系的新见解，因为它们揭示了非典型泛素链的作用、底物和 E3 调节的新机制，以及泛素化酶之间的广泛串扰。在这里，我们综述了这些新兴的泛素依赖性细胞周期控制的调节机制，并讨论了它们的操纵如何在未来提供治疗益处。
