COP9信号体
NEDD8公司
卡林
泛素
生物
细胞生物学
癌变
癌细胞
细胞周期
癌症
调节器
癌症研究
泛素连接酶
生物化学
遗传学
蛋白酶
酶
基因
肽水解酶类
作者
Wen‐Qi Du,Ruicheng Zhang,Bilal Muhammad,Dong‐Sheng Pei
标识
DOI:10.20892/j.issn.2095-3941.2021.0605
摘要
The COP9 signalosome (CSN) is a highly conserved protein complex composed of 8 subunits (CSN1 to CSN8). The individual subunits of the CSN play essential roles in cell proliferation, tumorigenesis, cell cycle regulation, DNA damage repair, angiogenesis, and microenvironmental homeostasis. The CSN complex has an intrinsic metalloprotease that removes the ubiquitin-like activator NEDD8 from cullin-RING ligases (CRLs). Binding of neddylated CRLs to CSN is sensed by CSN4 and communicated to CSN5 with the assistance of CSN6, thus leading to the activation of deneddylase. Therefore, CSN is a crucial regulator at the intersection between neddylation and ubiquitination in cancer progression. Here, we summarize current understanding of the roles of individual CSN subunits in cancer progression. Furthermore, we explain how the CSN affects tumorigenesis through regulating transcription factors and the cell cycle. Finally, we discuss individual CSN subunits as potential therapeutic targets to provide new directions and strategies for cancer therapy.
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