COP9 信号体：Cullin-RING 连接酶的多功能调节枢纽。

The COP9 signalosome: A versatile regulatory hub of Cullin-RING ligases.

机构信息

Institute of Experimental Internal Medicine, Medical Faculty, Otto von Guericke University, 39120 Magdeburg, Germany.

出版信息

Trends Biochem Sci. 2023 Jan;48(1):82-95. doi: 10.1016/j.tibs.2022.08.003. Epub 2022 Aug 27.

DOI:10.1016/j.tibs.2022.08.003

PMID:36041947

Abstract

The COP9 signalosome (CSN) is a universal regulator of Cullin-RING ubiquitin ligases (CRLs) - a family of modular enzymes that control various cellular processes via timely degradation of key signaling proteins. The CSN, with its eight-subunit architecture, employs multisite binding of CRLs and inactivates CRLs by removing a small ubiquitin-like modifier named neural precursor cell-expressed, developmentally downregulated 8 (Nedd8). Besides the active site of the catalytic subunit CSN5, two allosteric sites are present in the CSN, one of which recognizes the substrate recognition module and the presence of CRL substrates, and the other of which can 'glue' the CSN-CRL complex by recruitment of inositol hexakisphosphate. In this review, we present recent findings on the versatile regulation of CSN-CRL complexes.

摘要

COP9 信号体（CSN）是一种普遍的 Cullin-RING 泛素连接酶（CRL）的调节剂 - CRL 是一类模块化的酶，通过及时降解关键信号蛋白来控制各种细胞过程。CSN 具有八亚基结构，通过多部位结合 CRL 并去除一种名为神经前体细胞表达的、发育下调的 8（Nedd8）的小泛素样修饰物来使 CRL 失活。除了催化亚基 CSN5 的活性位点外，CSN 中还存在两个变构位点，其中一个识别底物识别模块和 CRL 底物的存在，另一个通过募集肌醇六磷酸可以“粘合”CSN-CRL 复合物。在这篇综述中，我们介绍了关于 CSN-CRL 复合物的多功能调节的最新发现。