- Source: COP9 signalosome
- COP9 signalosome
- Signalosome
- COP9 signalosome complex subunit 3
- COP9 constitutive photomorphogenic homolog subunit 5
- COPS7B
- COPS7A
- CSN
- Interferon
- COPS8
- COPS4
Artikel: COP9 signalosome GudangMovies21 Rebahinxxi
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. The complex was originally identified in plants, and subsequently found in all eukaryotic organisms including human.
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.
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.
References
Further reading
Salmena, Leonardo; Hakem, Razqallah (2013). "From photomorphogenesis to cancer. A CSN journey". Cell Cycle. 12 (2): 205–206. doi:10.4161/cc.23422. PMC 3575449. PMID 23287466.
Singer, R.; Atar, S.; Atias, O.; Oron, E.; Segal, D.; Hirsch, J. A.; Chamovitz, D. A. (2014). "Drosophila COP9 signalosome subunit 7 interacts with multiple genomic loci to regulate development". Nucleic Acids Research. 42 (15): 9761–9770. doi:10.1093/nar/gku723. PMC 4150811. PMID 25106867.
Lingaraju, G. M.; Bunker, R. D.; Cavadini, S.; Hess, D.; Hassiepen, U.; Renatus, M.; Thomä, N. H. (2014). "Crystal structure of the human COP9 signalosome". Nature. 512 (7513): 161–165. Bibcode:2014Natur.512..161L. doi:10.1038/nature13566. PMID 25043011. S2CID 205239748.
Birol, M.; Echalier, A.; Dumas, C.; Padilla, A.; Yang, Y.; Hoh, F. (2014). "The COP9 Signalosome: Activity and Regulation". Biophysical Journal. 106 (2): 463a. Bibcode:2014BpJ...106..463B. doi:10.1016/j.bpj.2013.11.2622.
Chamovitz, D. A. (2009). "Revisiting the COP9 signalosome as a transcriptional regulator". EMBO Reports. 10 (4): 352–358. doi:10.1038/embor.2009.33. PMC 2672896. PMID 19305390.
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. PMID 22325866.
Fang, L.; Kaake, R. M.; Patel, V. R.; Yang, Y.; Baldi, P.; Huang, L. (2012). "Mapping the Protein Interaction Network of the Human COP9 Signalosome Complex Using a Label-free QTAX Strategy". Molecular & Cellular Proteomics. 11 (5): 138–147. doi:10.1074/mcp.M111.016352. PMC 3418852. PMID 22474085.