Institute of Experimental Internal Medicine, Medical Faculty, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany.
School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiang'an South Road, Xiamen 361102, China.
Biomolecules. 2020 Jul 21;10(7):1082. doi: 10.3390/biom10071082.
The COP9 signalosome (CSN) is a signaling platform controlling the cellular ubiquitylation status. It determines the activity and remodeling of ~700 cullin-RING ubiquitin ligases (CRLs), which control more than 20% of all ubiquitylation events in cells and thereby influence virtually any cellular pathway. In addition, it is associated with deubiquitylating enzymes (DUBs) protecting CRLs from autoubiquitylation and rescuing ubiquitylated proteins from degradation. The coordination of ubiquitylation and deubiquitylation by the CSN is presumably important for fine-tuning the precise formation of defined ubiquitin chains. Considering its intrinsic DUB activity specific for deneddylation of CRLs and belonging to the JAMM family as well as its associated DUBs, the CSN represents a multi-DUB complex. Two CSN-associated DUBs, the ubiquitin-specific protease 15 (USP15) and USP48 are regulators in the NF-κB signaling pathway. USP15 protects CRL1 responsible for IκBα ubiquitylation, whereas USP48 stabilizes the nuclear pool of the NF-κB transcription factor RelA upon TNF stimulation by counteracting CRL2. Moreover, the CSN controls the neddylation status of cells by its intrinsic DUB activity and by destabilizing the associated deneddylation enzyme 1 (DEN1). Thus, the CSN is a master regulator at the intersection between ubiquitylation and neddylation.
COP9 信号体（CSN）是一个信号平台，控制着细胞的泛素化状态。它决定了大约 700 种 Cullin-RING 泛素连接酶（CRL）的活性和重塑，这些酶控制着细胞中超过 20%的所有泛素化事件，从而影响到几乎任何细胞途径。此外，它与去泛素化酶（DUBs）相关联，这些酶保护 CRL 免受自身泛素化，并将泛素化的蛋白质从降解中拯救出来。CSN 对泛素化和去泛素化的协调，可能对精细调节特定泛素链的形成非常重要。考虑到其对 CRL 去 neddylation 的固有 DUB 活性，以及其属于 JAMM 家族的特性，以及与之相关的 DUBs，CSN 代表了一个多 DUB 复合物。CSN 相关的两个 DUBs，即泛素特异性蛋白酶 15（USP15）和 USP48，是 NF-κB 信号通路的调节剂。USP15 保护负责 IκBα泛素化的 CRL1，而 USP48 通过对抗 CRL2，稳定 TNF 刺激后核内 NF-κB 转录因子 RelA 的池。此外，CSN 通过其内在的 DUB 活性和破坏相关的去 neddylation 酶 1（DEN1）来控制细胞的 neddylation 状态。因此，CSN 是泛素化和 neddylation 交汇点的主要调控因子。
