Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, 20892-4255, USA.
Exp Mol Med. 2020 Oct;52(10):1637-1651. doi: 10.1038/s12276-020-00508-4. Epub 2020 Oct 2.
The last decade has revealed new roles for Cullin-RING ubiquitin ligases (CRLs) in a myriad of cellular processes, including cell cycle progression. In addition to CRL1, also named SCF (SKP1-Cullin 1-F box protein), which has been known for decades as an important factor in the regulation of the cell cycle, it is now evident that all eight CRL family members are involved in the intricate cellular pathways driving cell cycle progression. In this review, we summarize the structure of CRLs and their functions in driving the cell cycle. We focus on how CRLs target key proteins for degradation or otherwise alter their functions to control the progression over the various cell cycle phases leading to cell division. We also summarize how CRLs and the anaphase-promoting complex/cyclosome (APC/C) ligase complex closely cooperate to govern efficient cell cycle progression.
过去十年揭示了 Cullin-RING 泛素连接酶 (CRLs) 在众多细胞过程中的新作用,包括细胞周期进程。除了数十年来一直被认为是调节细胞周期的重要因素的 CRL1(也称为 SCF[SKP1-Cullin1-F 盒蛋白])之外,现在显然所有八个 CRL 家族成员都参与了驱动细胞周期进程的复杂细胞途径。在这篇综述中,我们总结了 CRL 的结构及其在驱动细胞周期中的功能。我们重点介绍了 CRL 如何靶向关键蛋白质进行降解,或者通过其他方式改变它们的功能,以控制各种细胞周期阶段的进展,从而导致细胞分裂。我们还总结了 CRL 和后期促进复合物/周期蛋白 (APC/C) 连接酶复合物如何密切合作以有效地控制细胞周期进程。