COP9 signalosome subunit 2 (COPS2)

COP9 signalosome subunit 2 (COPS2) is a core protein of the COP9 signalosome, an evolutionarily conserved eight-subunit complex that regulates protein turnover by mediating deneddylation of cullin-RING ubiquitin ligases (CRLs). As a transcriptional corepressor, COPS2 binds nuclear hormone receptors and other transcriptional regulators, facilitating gene expression control. In embryonic stem cells, COPS2 maintains pluripotency and cell cycle progression by preventing the proteasomal degradation of Nanog and other critical factors. It also interacts with oncogenic transcription factors (e.g., Snail), influencing tumorigenic signaling pathways. Upregulation and deregulation of COPS2 are implicated in cancer progression, including colorectal and hepatocellular carcinomas, and the protein also plays roles in DNA repair, neuronal differentiation, and early development. Systemic disruption of COPS2 has pronounced effects, including cell cycle arrest and embryonic lethality, making it a promising but challenging therapeutic target[1][2][3][4][5][7].

Other names

COP9 signalosome complex subunit 2CSN2TRIP15SGN2Signalosome subunit 2TR-interacting protein 15Alien homologThyroid receptor-interacting protein 15TRIP-15ALIENJAB1-containing signalosome subunit 2

Drugs targeting the COP9 signalosome would inhibit its protein-deneddylation activity, leading to increased ubiquitin ligase activity and altered protein degradation (especially of oncogenes and tumor suppressors). Indirect regulation of protein turnover (degradation of transcription factors such as Snail, Nanog).