COP9 (Constitutive photomorphogenesis 9) signalosome (CSN) is aprotein complex withisopeptidase activity. It catalyses the hydrolysis ofNEDD8 protein from the cullin subunit ofCullin-RING ubiquitin ligases (CRL). Therefore, it is responsible for CRLdeneddylation – 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 ~350kDa) 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]
COP9 signalosome as a drug target for cancer and parasitic infections
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.
