PT  - JOURNAL ARTICLE
AU  - Wenqi Du
AU  - Ruicheng Zhang
AU  - Bilal Muhammad
AU  - Dongsheng Pei
TI  - Targeting the COP9 signalosome for cancer therapy
AID  - 10.20892/j.issn.2095-3941.2021.0605
DP  - 2022 May 15
TA  - Cancer Biology & Medicine
PG  - 573--590
VI  - 19
IP  - 5
4099  - http://www.cancerbiomed.org/content/19/5/573.short
4100  - http://www.cancerbiomed.org/content/19/5/573.full
SO  - Cancer Biology & Medicine2022 May 15; 19
AB  - 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.