Lydeard John R, Schulman Brenda A, Harper J Wade
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
EMBO Rep. 2013 Dec;14(12):1050-61. doi: 10.1038/embor.2013.173. Epub 2013 Nov 15.
Cullin-RING E3 ubiquitin ligases (CRLs) control a plethora of biological pathways through targeted ubiquitylation of signalling proteins. These modular assemblies use substrate receptor modules to recruit specific targets. Recent efforts have focused on understanding the mechanisms that control the activity state of CRLs through dynamic alterations in CRL architecture. Central to these processes are cycles of cullin neddylation and deneddylation, as well as exchange of substrate receptor modules to re-sculpt the CRL landscape, thereby responding to the cellular requirements to turn over distinct proteins in different contexts. This review is focused on how CRLs are dynamically controlled with an emphasis on how cullin neddylation cycles are integrated with receptor exchange.
Cullin-RING E3泛素连接酶（CRLs）通过对信号蛋白进行靶向泛素化来控制众多生物学途径。这些模块化组件利用底物受体模块招募特定靶点。最近的研究工作集中在理解通过CRL结构的动态改变来控制CRLs活性状态的机制。这些过程的核心是cullin的类泛素化修饰和去类泛素化修饰循环，以及底物受体模块的交换以重塑CRL格局，从而响应细胞在不同情况下清除不同蛋白质的需求。本综述重点关注CRLs如何被动态控制，尤其强调cullin类泛素化修饰循环如何与受体交换相结合。
