Department of Biochemistry, Institute for Aging and Metabolic Diseases, College of Medicine, The Catholic University of Korea, Seoul 06592, Republic of Korea.
Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
Biochim Biophys Acta Rev Cancer. 2022 Nov;1877(6):188824. doi: 10.1016/j.bbcan.2022.188824. Epub 2022 Oct 12.
The Anaphase-Promoting Complex/Cyclosome (APC/C), an E3 ubiquitin ligase, and two co-activators, Cdc20 and Cdh1, enable the ubiquitin-dependent proteasomal degradation of various critical cell cycle regulators and govern cell division in a timely and precise manner. Dysregulated cell cycle events cause uncontrolled cell proliferation, leading to tumorigenesis. Studies have shown that Cdh1 has tumor suppressive activities while Cdc20 has an oncogenic property, suggesting that Cdc20 is an emerging therapeutic target for cancer treatment. Therefore, in this review, we discussed recent findings about the essential roles of APC/C-Cdc20 in cell cycle regulation. Furthermore, we briefly summarized that the regulation of Cdc20 expression levels is strictly controlled to order cell cycle events appropriately. Finally, given the function of Cdc20 as an oncogene, therapeutic interventions targeting Cdc20 activity may be beneficial in cancer treatment.
后期促进复合物/细胞周期蛋白体(APC/C)是一种 E3 泛素连接酶,与两个辅激活因子 Cdc20 和 Cdh1 一起,使各种关键细胞周期调控因子能够进行依赖泛素的蛋白酶体降解,并以精确的时间方式控制细胞分裂。细胞周期事件失调会导致不受控制的细胞增殖,从而导致肿瘤发生。研究表明,Cdh1 具有肿瘤抑制活性,而 Cdc20 具有致癌特性,这表明 Cdc20 是癌症治疗的一个新兴治疗靶点。因此,在这篇综述中,我们讨论了 APC/C-Cdc20 在细胞周期调控中的重要作用的最新发现。此外,我们简要总结了 Cdc20 表达水平的调节受到严格控制,以适当安排细胞周期事件。最后,鉴于 Cdc20 作为癌基因的功能,针对 Cdc20 活性的治疗干预可能有益于癌症治疗。