Department of Cellular Biology, University of Georgia, 724 Biological Sciences Bldg,, Athens, GA 30602-2607, USA.
Cell Div. 2008 Feb 18;3:7. doi: 10.1186/1747-1028-3-7.
Cullin-RING ubiquitin ligases (CRLs) comprise the largest known category of ubiquitin ligases. CRLs regulate an extensive number of dynamic cellular processes, including multiple aspects of the cell cycle, transcription, signal transduction, and development. CRLs are multisubunit complexes composed of a cullin, RING H2 finger protein, a variable substrate-recognition subunit (SRS), and for most CRLs, an adaptor that links the SRS to the complex. Eukaryotic species contain multiple cullins, with five major types in metazoa. Each cullin forms a distinct class of CRL complex, with distinct adaptors and/or substrate-recognition subunits. Despite this diversity, each of the classes of CRL complexes is subject to similar regulatory mechanisms. This review focuses on the global regulation of CRL complexes, encompassing: neddylation, deneddylation by the COP9 Signalosome (CSN), inhibitory binding by CAND1, and the dimerization of CRL complexes. We also address the role of cycles of activation and inactivation in regulating CRL activity and switching between substrate-recognition subunits.
Cullin-RING 泛素连接酶（CRLs）构成了已知最大的泛素连接酶类别。CRLs 调节广泛的动态细胞过程，包括细胞周期、转录、信号转导和发育的多个方面。CRLs 是多亚基复合物，由一个 cullin、RING H2 指状蛋白、一个可变的底物识别亚基（SRS）组成，对于大多数 CRL 而言，还有一个衔接子将 SRS 连接到复合物上。真核生物物种含有多种 cullins，在后生动物中有五种主要类型。每个 cullin 形成一个独特的 CRL 复合物类，具有不同的衔接子和/或底物识别亚基。尽管存在这种多样性，但每一类 CRL 复合物都受到相似的调节机制的影响。这篇综述重点讨论了 CRL 复合物的全局调节，包括：neddylation、COP9 信号体（CSN）介导的去 neddylation、CAND1 的抑制性结合以及 CRL 复合物的二聚化。我们还探讨了激活和失活循环在调节 CRL 活性和切换底物识别亚基方面的作用。
