Yu Hongtao
Department of Pharmacology, The University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390-9041, USA.
Mol Cell. 2007 Jul 6;27(1):3-16. doi: 10.1016/j.molcel.2007.06.009.
Cdc20 is an essential cell-cycle regulator required for the completion of mitosis in organisms from yeast to man and contains at its C terminus a WD40 repeat domain that mediates protein-protein interactions. In mitosis, Cdc20 binds to and activates the ubiquitin ligase activity of a large molecular machine called the anaphase-promoting complex/cyclosome (APC/C) and enables the ubiquitination and degradation of securin and cyclin B, thus promoting the onset of anaphase and mitotic exit. APC/C(Cdc20) is temporally and spatially regulated during the somatic and embryonic cell cycle by numerous mechanisms, including the spindle checkpoint and the cytostatic factor (CSF). Therefore, Cdc20 serves as an integrator of multiple intracellular signaling cascades that regulate progression through mitosis. This review summarizes recent progress toward the understanding of the functions of Cdc20, the mechanisms by which it activates APC/C, and its regulation by phosphorylation and by association with its binding proteins.
Cdc20是从酵母到人类等生物体完成有丝分裂所必需的细胞周期调节因子,其C端含有一个介导蛋白质-蛋白质相互作用的WD40重复结构域。在有丝分裂过程中,Cdc20结合并激活一种称为后期促进复合物/细胞周期体(APC/C)的大分子机器的泛素连接酶活性,使securin和细胞周期蛋白B发生泛素化和降解,从而促进后期的开始和有丝分裂退出。在体细胞和胚胎细胞周期中,APC/C(Cdc20)通过多种机制在时间和空间上受到调控,包括纺锤体检查点和细胞静止因子(CSF)。因此,Cdc20作为多个细胞内信号级联反应的整合者,调节有丝分裂的进程。本综述总结了在理解Cdc20的功能、其激活APC/C的机制以及其通过磷酸化和与其结合蛋白的结合进行调控方面的最新进展。