Targeting the COP9 signalosome for cancer therapy

• Published in: Cancer biology & medicine Vol. 19; no. 5; pp. 573 - 590
• Main Authors: Du, Wenqi, Zhang, Ruicheng, Muhammad, Bilal, Pei, Dongsheng
• Format: Journal Article
• Language: English
• Published: China Department of Human Anatomy,Xuzhou Medical University,Xuzhou 221004,China%Department of Neurology,Affiliated Hospital of Xuzhou Medical University,Xuzhou 221006,China%Department of Pathology,Xuzhou Medical University,Xuzhou 221004,China 21.03.2022; Department of Pathology,Xuzhou Medical University,Xuzhou 221004,China; Compuscript; China Anti-Cancer Association
• Subjects: cell proliferation; cop9 signalosome; cullin-ring ligases; Review; tumorigenesis; ubiquitin; COP9 signalosome; tumorigenesis; cell proliferation; cullin-RING ligases; ubiquitin
• ISSN: 2095-3941
• DOI: 10.20892/j.issn.2095-3941.2021.0605

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.