Disease relevance of COPS3

• Amplification and overexpression of COPS3 in osteosarcomas potentially target TP53 for proteasome-mediated degradation [1].

High impact information on COPS3

• A reduction in the level of CSN3 protein with small interfering RNA abrogated MLF1-induced G1 arrest and impaired the activation of p53 by genotoxic stress [2].
• CK2 binds to DeltaCSN3(111-403) and CSN7, whereas PKD interacts with full-length CSN3 [3].
• The biologic relevance of the interaction between icIL-1Ra1 and CSN3 was demonstrated in the keratinocyte cell lines KB and A431, both possessing abundant CSN3 [4].
• Thus, icIL-1Ra1 exhibits unique anti-inflammatory properties inside cells through binding to CSN3 with subsequent inhibition of the p38 MAPK signal transduction pathway [4].
• A yeast two-hybrid screen with HeLa cell lysates revealed specific binding of icIL-1Ra1, and not of the other IL-1Ra isoforms, to the third component of the COP9 signalosome complex (CSN3) [4].

Biological context of COPS3

• Genes PMP22 and COPS3 and three expressed sequence tags from within 17p11.2 ~ p12 have been found to be frequently overexpressed and consistently overexpressed after amplification, which identifies them as candidate oncogenes in this region [5].
• Overexpression of COPS3 has been linked to TP53 protein degradation and, being equivalent to TP53 mutation, the induction of genomic instability, which frequently occurs in high-grade osteosarcoma [5].
• Our findings suggest that the abnormalities in the circadian rhythm of melatonin and altered sleep patterns could be secondary to aberrations in the production, secretion, distribution, or metabolism of melatonin; however, a direct role for COPS3 could not be established [6].
• To investigate a potential correlation of COPS3 haploinsufficiency and disturbed melatonin excretion, we performed fluorescence in situ hybridisation (FISH) using two BACs containing coding exons of COPS3 [6].
• We assessed the potential effect of haploinsufficiency of SGN3 in SMS patient lymphoblastoid cell lines through transfection studies and western analysis [7].

Associations of COPS3 with chemical compounds

• All patients studied, including the one patient with a normal melatonin rhythm, were haploinsufficient for COPS3 [6].
• Overexpression of CSN3 inhibits NF-kappaB activation triggered by tumor necrosis factor (TNF), but not interleukin-1 (IL-1) [8].

Other interactions of COPS3

• The present study shows that COPS3, located in 17p11 and encoding a component of the proteasome pathway, is more frequently amplified in osteosarcomas (OS) than is MDM2 [1].
• The results of transient expression experiments in COS7 cells confirmed the interaction of Int-6 with Rpt4, CSN3 and CSN6, but also showed that Int-6 is able to bind another subunit of the CSN: CSN7a [9].

References