COP9 (Constitutive photomorphogenesis 9) signalosome (CSN) is a protein complex with isopeptidase activity. It catalyses the hydrolysis of NEDD8 protein from the cullin subunit of Cullin-RING ubiquitin ligases (CRL). Therefore, it is responsible for CRL deneddylation – at the same time, it is able to bind denedyllated cullin-RING complex and retain them in deactivated form. COP9 signalosome thus serves as a sole deactivator of CRLs.[1] The complex was originally identified in plants,[2][3] and subsequently found in all eukaryotic organisms including human. [4][5] Human COP9 signalosome (total size ~350 kDa) consists of 8 subunits - CSN1, CSN2, CSN3, CSN4, CSN5, CSN6, CSN7 (COPS7A, COPS7B), CSN8. All are essential for full function of the complex and mutation in some of them is lethal in mice.[1]
Given the essential functions of the COP9 signalosome, the complex has been explored as a target for drug discovery. Preclinical studies showed that inhibiting COP9 resulted in death of cancer cells and medically important parasite.[6][7]
Wei, N; Serino, G; Deng, XW (December 2008). "The COP9 signalosome: more than a protease". Trends in Biochemical Sciences. 33 (12): 592–600. doi:10.1016/j.tibs.2008.09.004. PMID18926707.
Stratmann, Johannes W.; Gusmaroli, Giuliana (2012). "Many jobs for one good cop – The COP9 signalosome guards development and defense". Plant Science. 185–186: 50–64. doi:10.1016/j.plantsci.2011.10.004. PMID22325866.
