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Gene Review

COPS3  -  COP9 signalosome subunit 3

Homo sapiens

Synonyms: COP9 signalosome complex subunit 3, CSN3, JAB1-containing signalosome subunit 3, SGN3, Signalosome subunit 3
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Disease relevance of COPS3


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].


  1. Amplification and overexpression of COPS3 in osteosarcomas potentially target TP53 for proteasome-mediated degradation. Henriksen, J., Aagesen, T.H., Maelandsmo, G.M., Lothe, R.A., Myklebost, O., Forus, A. Oncogene (2003) [Pubmed]
  2. Myeloid leukemia factor 1 regulates p53 by suppressing COP1 via COP9 signalosome subunit 3. Yoneda-Kato, N., Tomoda, K., Umehara, M., Arata, Y., Kato, J.Y. EMBO J. (2005) [Pubmed]
  3. Protein kinase CK2 and protein kinase D are associated with the COP9 signalosome. Uhle, S., Medalia, O., Waldron, R., Dumdey, R., Henklein, P., Bech-Otschir, D., Huang, X., Berse, M., Sperling, J., Schade, R., Dubiel, W. EMBO J. (2003) [Pubmed]
  4. Intracellular IL-1 receptor antagonist type 1 inhibits IL-1-induced cytokine production in keratinocytes through binding to the third component of the COP9 signalosome. Banda, N.K., Guthridge, C., Sheppard, D., Cairns, K.S., Muggli, M., Bech-Otschir, D., Dubiel, W., Arend, W.P. J. Immunol. (2005) [Pubmed]
  5. Amplification and overexpression of genes in 17p11.2 ~ p12 in osteosarcoma. van Dartel, M., Hulsebos, T.J. Cancer Genet. Cytogenet. (2004) [Pubmed]
  6. Circadian rhythm abnormalities of melatonin in Smith-Magenis syndrome. Potocki, L., Glaze, D., Tan, D.X., Park, S.S., Kashork, C.D., Shaffer, L.G., Reiter, R.J., Lupski, J.R. J. Med. Genet. (2000) [Pubmed]
  7. Hemizygosity for the COP9 signalosome subunit gene, SGN3, in the Smith-Magenis syndrome. Elsea, S.H., Mykytyn, K., Ferrell, K., Coulter, K.L., Das, P., Dubiel, W., Patel, P.I., Metherall, J.E. Am. J. Med. Genet. (1999) [Pubmed]
  8. CSN3 interacts with IKKgamma and inhibits TNF- but not IL-1-induced NF-kappaB activation. Hong, X., Xu, L., Li, X., Zhai, Z., Shu, H. FEBS Lett. (2001) [Pubmed]
  9. Association of the mammalian proto-oncoprotein Int-6 with the three protein complexes eIF3, COP9 signalosome and 26S proteasome. Hoareau Alves, K., Bochard, V., Réty, S., Jalinot, P. FEBS Lett. (2002) [Pubmed]
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