Gene Symbol: COPS3
Description: COP9 signalosome subunit 3
Alias: CSN3, SGN3, COP9 signalosome complex subunit 3, COP9 complex subunit 3, COP9 constitutive photomorphogenic homolog subunit 3, JAB1-containing signalosome subunit 3, signalosome subunit 3
Species: human
Products:     COPS3

Top Publications

  1. Henriksen J, Aagesen T, Maelandsmo G, Lothe R, Myklebost O, Forus A. Amplification and overexpression of COPS3 in osteosarcomas potentially target TP53 for proteasome-mediated degradation. Oncogene. 2003;22:5358-61 pubmed
    ..The present study shows that COPS3, located in 17p11 and encoding a component of the proteasome pathway, is more frequently amplified in ..
  2. Yang X, Menon S, Lykke Andersen K, Tsuge T, Di Xiao -, Wang X, et al. The COP9 signalosome inhibits p27(kip1) degradation and impedes G1-S phase progression via deneddylation of SCF Cul1. Curr Biol. 2002;12:667-72 pubmed
    ..We conclude that CSN inhibits SCF ubiquitin ligase activity in targeting p27 proteolysis and negatively regulates cell cycle at the G1 phase by promoting deneddylation of Cul1. ..
  3. Min K, Kwon M, Park H, Park Y, Yoon S, Yoon J. CAND1 enhances deneddylation of CUL1 by COP9 signalosome. Biochem Biophys Res Commun. 2005;334:867-74 pubmed
    ..Our data suggest that enhancement of CSN-mediated deneddylation by CAND1 may contribute to its function as a positive regulator of SCFs in vivo. ..
  4. Groisman R, Polanowska J, Kuraoka I, Sawada J, Saijo M, Drapkin R, et al. The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. Cell. 2003;113:357-67 pubmed
    ..Knockdown of CSN with RNA interference leads to defects in NER. These results suggest that the distinct UV response of the DDB2 and CSA complexes is involved in diverse mechanisms of NER. ..
  5. Uhle S, Medalia O, Waldron R, Dumdey R, Henklein P, Bech Otschir D, et al. Protein kinase CK2 and protein kinase D are associated with the COP9 signalosome. EMBO J. 2003;22:1302-12 pubmed
    ..CK2 binds to DeltaCSN3(111-403) and CSN7, whereas PKD interacts with full-length CSN3. CK2 phosphorylates CSN2 and CSN7, and PKD modifies CSN7. Both CK2 and PKD phosphorylate c-Jun as well as p53...
  6. Pick E, Lau O, Tsuge T, Menon S, Tong Y, Dohmae N, et al. Mammalian DET1 regulates Cul4A activity and forms stable complexes with E2 ubiquitin-conjugating enzymes. Mol Cell Biol. 2007;27:4708-19 pubmed
    ..Overexpression of DET1 inhibits UV-induced CDT1 degradation in cultured cells. These findings demonstrate that the conserved DET1 complex modulates Cul4A functions by a novel mechanism. ..
  7. Bech Otschir D, Kraft R, Huang X, Henklein P, Kapelari B, Pollmann C, et al. COP9 signalosome-specific phosphorylation targets p53 to degradation by the ubiquitin system. EMBO J. 2001;20:1630-9 pubmed
    ..It induces the cyclin-dependent inhibitor p21. In HeLa and MCF-7 cells, inhibition of CSN kinase by curcumin or Deltap53(145-164) results in accumulation of endogenous p53. ..
  8. Lyapina S, Cope G, Serino G, Tsuge T, Zhou C, Wolf D, et al. Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome. Science. 2001;292:1382-5 pubmed
  9. Huang X, Langelotz C, Hetfeld Pechoc B, Schwenk W, Dubiel W. The COP9 signalosome mediates beta-catenin degradation by deneddylation and blocks adenomatous polyposis coli destruction via USP15. J Mol Biol. 2009;391:691-702 pubmed publisher
    ..A model is provided that proposes a role of CSN-mediated deneddylation in the formation of the beta-catenin-degrading supercomplex and the protection of complex-bound APC via CSN-associated USP15. ..

More Information


  1. Sharon M, Mao H, Boeri Erba E, Stephens E, Zheng N, Robinson C. Symmetrical modularity of the COP9 signalosome complex suggests its multifunctionality. Structure. 2009;17:31-40 pubmed publisher
    ..This suggests that the propensity of the CSN complex to change and adapt its subunit composition might underlie its ability to perform multiple functions in vivo. ..
  2. Yan T, Wunder J, Gokgoz N, Gill M, Eskandarian S, Parkes R, et al. COPS3 amplification and clinical outcome in osteosarcoma. Cancer. 2007;109:1870-6 pubmed
    Amplification of several genes that map to a region of chromosome 17p11.2, including COPS3, was observed in high-grade osteosarcoma. These genes were also shown to be overexpressed and may be involved in osteosarcoma tumorigenesis...
  3. Huang X, Hetfeld B, Seifert U, Kahne T, Kloetzel P, Naumann M, et al. Consequences of COP9 signalosome and 26S proteasome interaction. FEBS J. 2005;272:3909-17 pubmed
    ..The possible role of super-complexes composed of the CSN, the 26S proteasome and of Ub ligases in the regulation of protein stability is discussed. ..
  4. Tsuge T, Matsui M, Wei N. The subunit 1 of the COP9 signalosome suppresses gene expression through its N-terminal domain and incorporates into the complex through the PCI domain. J Mol Biol. 2001;305:1-9 pubmed
    ..demonstrated that the C-terminal half of CSN1 encompassing the PCI domain is responsible for interaction with CSN2, CSN3, and CSN4 subunits and is required for incorporation of the subunit into the complex...
  5. Yan T, Tang G, Ren T, Shen D, Sun K, Liang W, et al. RNAi-mediated COPS3 gene silencing inhibits metastasis of osteogenic sarcoma cells. Cancer Gene Ther. 2011;18:450-6 pubmed publisher
    ..In this study, we aimed to identify the relationship of COPS3 gene expression to metastasis...
  6. Emberley E, Mosadeghi R, Deshaies R. Deconjugation of Nedd8 from Cul1 is directly regulated by Skp1-F-box and substrate, and the COP9 signalosome inhibits deneddylated SCF by a noncatalytic mechanism. J Biol Chem. 2012;287:29679-89 pubmed publisher
    ..Upon consumption of substrate and subsequent deneddylation, CSN can remain stably bound to the CRL and hold it in low state of reduced activity. ..
  7. Lingaraju G, Bunker R, Cavadini S, Hess D, Hassiepen U, Renatus M, et al. Crystal structure of the human COP9 signalosome. Nature. 2014;512:161-5 pubmed publisher
    ..We find that neddylated CRL binding to CSN is sensed by CSN4, and communicated to CSN5 with the assistance of CSN6, resulting in activation of the deneddylase. ..
  8. Arora R, Sharma A, Sharma U, Girdhar Y, Kaur M, Kapoor P, et al. Buffalo milk transcriptome: A comparative analysis of early, mid and late lactation. Sci Rep. 2019;9:5993 pubmed publisher
    ..5% and 75.7% respectively. Highly expressed genes (RPKM > 3000), throughout lactation included CSN2, CSN1S1, CSN3, LALBA, SPP1 and TPT1...
  9. Bonfatti V, Cecchinato A, Carnier P. Short communication: predictive ability of Fourier-transform mid-infrared spectroscopy to assess CSN genotypes and detailed protein composition of buffalo milk. J Dairy Sci. 2015;98:6583-7 pubmed publisher
    ..Contents of protein fractions, as well as CSN1S1 and CSN3 genotypes, were assessed by reversed phase HPLC...
  10. Zarich N, Anta B, Fernández Medarde A, Ballester A, de Lucas M, Cámara A, et al. The CSN3 subunit of the COP9 signalosome interacts with the HD region of Sos1 regulating stability of this GEF protein. Oncogenesis. 2019;8:2 pubmed publisher
    ..Using a yeast two-hybrid system, we identified the interaction between the Sos1 HD region and CSN3, the third component of the COP9 signalosome, a conserved, multi-subunit protein complex that functions in the ..
  11. Molzan M, Ottmann C. Subcellular localization of full-length human myeloid leukemia factor 1 (MLF1) is independent of 14-3-3 proteins. Cell Mol Biol Lett. 2013;18:137-48 pubmed publisher
    ..function of MLF1 is limited and mostly derived from studies identifying MLF1 interaction partners like CSN3, MLF1IP, MADM, Manp and the 14-3-3 proteins...
  12. Miluchová M, Gábor M, Candrák J, Trakovická A, Candráková K. Association of HindIII-polymorphism in kappa-casein gene with milk, fat and protein yield in holstein cattle. Acta Biochim Pol. 2018;65:403-407 pubmed publisher
    ..3847) and level of possible variability realization (27.91%). The effect of polymorphism of CSN3 gene on average breeding values for milk production traits, such as yield of milk, fat and protein expressed in ..
  13. Zhang F, Yan T, Guo W, Sun K, Wang S, Bao X, et al. Novel oncogene COPS3 interacts with Beclin1 and Raf-1 to regulate metastasis of osteosarcoma through autophagy. J Exp Clin Cancer Res. 2018;37:135 pubmed publisher
    Expression of COP9 signalosome subunit 3 (COPS3), an oncogene overexpressed in osteosarcoma, has been demonstrated to be significantly correlated with tumor metastasis...
  14. Cieslak J, Wodas L, Borowska A, Pawlak P, Czyzak Runowska G, Wójtowski J, et al. 5'-flanking variants of equine casein genes (CSN1S1, CSN1S2, CSN2, CSN3) and their relationship with gene expression and milk composition. J Appl Genet. 2019;60:71-78 pubmed publisher
    ..screening for polymorphism in 5'-flanking regions of four genes encoding equine caseins (CSN1S1, CSN1S2, CSN2, and CSN3) and making a preliminary assessment of their effect on the gene expression (on the mRNA and protein levels) and ..
  15. Pegolo S, Bergamaschi M, Gasperi F, Biasioli F, Cecchinato A, Bittante G. Integrated PTR-ToF-MS, GWAS and biological pathway analyses reveal the contribution of cow's genome to cheese volatilome. Sci Rep. 2018;8:17002 pubmed publisher
    ..g. CSN3, GNRHR and FAM169A), fat (e.g. AGPAT3, SCD5, and GPAM) and carbohydrate (e.g. B3GNT2, B4GALT1, and PHKB) metabolism...
  16. Xiang R, Hayes B, Vander Jagt C, Macleod I, Khansefid M, Bowman P, et al. Genome variants associated with RNA splicing variations in bovine are extensively shared between tissues. BMC Genomics. 2018;19:521 pubmed publisher
    ..putative causal mutations were identified, including an sQTL at Chr6:87392580 within the 5th exon of kappa casein (CSN3) associated with milk production traits...
  17. Glantz M, Gustavsson F, Bertelsen H, Stålhammar H, Lindmark Månsson H, Paulsson M, et al. Bovine chromosomal regions affecting rheological traits in acid-induced skim milk gels. J Dairy Sci. 2015;98:1273-85 pubmed publisher
    ..and yield stress, the QTL identified with the most significant SNP closest to the gene coding for κ-casein (CSN3)...
  18. Pfister A, Barberon M, Alassimone J, Kalmbach L, Lee Y, Vermeer J, et al. A receptor-like kinase mutant with absent endodermal diffusion barrier displays selective nutrient homeostasis defects. elife. 2014;3:e03115 pubmed publisher
    ..In this study, we report the identification and characterization of a strong barrier mutant, schengen3 (sgn3)...
  19. Sanchez M, Wolf V, El Jabri M, Beuvier E, Rolet Repecaud O, Gaüzère Y, et al. Short communication: Confirmation of candidate causative variants on milk composition and cheesemaking properties in Montbéliarde cows. J Dairy Sci. 2018;101:10076-10081 pubmed publisher
    ..In each candidate gene, we identified the most plausible causative variant: 4 are missense in the ALPL, SLC26A4, CSN3, and SCD genes, 7 are located in 5'UTR (AGPAT6), 3' untranslated region (GPT), or upstream (CSN1S1, CSN1S2, PAEP, ..
  20. Wang K, Yan H, Xu H, Yang Q, Zhang S, Pan C, et al. A novel indel within goat casein alpha S1 gene is significantly associated with litter size. Gene. 2018;: pubmed publisher
    The ruminant casein gene family (CSNs, link as CSN1S1-CSN2-CSN1S2-CSN3) is characterized by diverse variations and has been extensively studied for ruminant milk traits, however, studies on insertion/deletion (indel) mutations within this ..
  21. Noce A, Pazzola M, Dettori M, Amills M, Castello A, Cecchinato A, et al. Variations at regulatory regions of the milk protein genes are associated with milk traits and coagulation properties in the Sarda sheep. Anim Genet. 2016;47:717-726 pubmed publisher
    ..Association analysis revealed the existence of significant associations of CSN1S2 and CSN3 genotypes with milk protein and casein contents...
  22. Ahmed A, Rahmatalla S, Bortfeldt R, Arends D, Reissmann M, Brockmann G. Milk protein polymorphisms and casein haplotypes in Butana cattle. J Appl Genet. 2017;58:261-271 pubmed publisher
    ..assess genetic variation that is characteristic for Butana cattle in the milk protein genes CSN1S1, CSN2, CSN1S2, CSN3, LALBA, and LGB...
  23. Hong Y, Huang X, An L, Ye H, Ma K, Zhang F, et al. Overexpression of COPS3 promotes clear cell renal cell carcinoma progression via regulation of Phospho-AKT(Thr308), Cyclin D1 and Caspase-3. Exp Cell Res. 2018;365:163-170 pubmed publisher
    The third subunit of the COP9 signalosome (COPS3) is associated with cell proliferation and tumorigenesis process in cancer...
  24. Crisà A, Ferré F, Chillemi G, Moioli B. RNA-Sequencing for profiling goat milk transcriptome in colostrum and mature milk. BMC Vet Res. 2016;12:264 pubmed
    ..CSN2, PAEP, CSN1S2, CSN3, LALBA, TPT1, FTH1, M-SAA3, SPP1, GLYCAM1, EEF1A1, CTSD, FASN, RPS29, CSN1S1, KRT19 and CHEK1 were found between ..
  25. Wicker C, Izumi T. Analysis of RNA expression of normal and cancer tissues reveals high correlation of COP9 gene expression with respiratory chain complex components. BMC Genomics. 2016;17:983 pubmed
    ..Expressions of seven of the COP9 genes (COPS2, COPS3, COPS4, COPS5, COPS6, COPS7A, and COPS8) were found to be highly synergistic in the normal tissues...
  26. Selvaggi M, D Alessandro A, Dario C. Comparative characteristics of DNA polymorphisms of κ-casein gene (CSN3) in the horse and donkey. Genet Mol Res. 2015;14:14567-75 pubmed publisher
    ..From this point of view these two single nucleotide polymorphisms and particularly the c.-36C>A one could be useful instruments for population studies. ..
  27. Perna A, Intaglietta I, Gambacorta E, Simonetti A. The influence of casein haplotype on quality, coagulation, and yield traits of milk from Italian Holstein cows. J Dairy Sci. 2016;99:3288-3294 pubmed publisher
    The aim of this work was to investigate the effect of casein haplotype (CSN1S1, CSN2, and CSN3) on quality, coagulation, and yield traits of milk from Italian Holstein cows...
  28. Ba M, Surina J, Singer C, Valencik M. Knockdown of subunit 3 of the COP9 signalosome inhibits C2C12 myoblast differentiation via NF-KappaB signaling pathway. BMC Pharmacol Toxicol. 2017;18:47 pubmed publisher
    The COP9 signalosome (CSN) is a conserved protein complex composed of 8 subunits designated CSN1-CSN8. CSN3 represents the third subunit of the CSN and maintains the integrity of the complex...
  29. Wang M, Ji Y, Wang C, Chen L, Wang H, Loor J. The preliminary study on the effects of growth hormone and insulin-like growth factor-I on κ-casein synthesis in bovine mammary epithelial cells in vitro. J Anim Physiol Anim Nutr (Berl). 2016;100:251-5 pubmed publisher
    ..The quantity of κ-casein protein was measured by ELISA, and the κ-casein gene (CSN3) expression was examined by real-time quantitative PCR (RT-qPCR)...
  30. Suarez Vega A, Gutiérrez Gil B, Arranz J. Transcriptome expression analysis of candidate milk genes affecting cheese-related traits in 2 sheep breeds. J Dairy Sci. 2016;99:6381-6390 pubmed publisher
    ..Among the highly expressed genes in both breeds were the genes encoding caseins and whey proteins (CSN2, CSN3, CSN1S1, ENSOARG00000005099/PAEP, CSN1S2, LALBA), genes related to lipid metabolism (BTN1A1, XDH, FASN, ADFP, SCD, ..
  31. Korczeniewska J, Barnes B. Corrected and Republished from: The COP9 Signalosome Interacts with and Regulates Interferon Regulatory Factor 5 Protein Stability. Mol Cell Biol. 2018;38: pubmed publisher
    ..b>CSN3 was identified as a direct interacting partner of IRF5, and knockdown of this subunit with small interfering RNAs (..
  32. Brinkmann J, Jagannathan V, Drogemuller C, Rieder S, Leeb T, Thaller G, et al. Genetic variability of the equine casein genes. J Dairy Sci. 2016;99:5486-5497 pubmed publisher, the open reading frames of the 4 casein genes CSN1S1 (?S1-casein), CSN2 (?-casein), CSN1S2 (?S2-casein), and CSN3 (?-casein) were resequenced in 253 horses of 14 breeds...
  33. Doblas V, Smakowska Luzan E, Fujita S, Alassimone J, Barberon M, Madalinski M, et al. Root diffusion barrier control by a vasculature-derived peptide binding to the SGN3 receptor. Science. 2017;355:280-284 pubmed publisher
    ..A factor responsible for their establishment is the SCHENGEN3/GASSHO1 (SGN3/GSO1) receptor-like kinase. Its loss of function causes discontinuous Casparian strips...
  34. Wang Q, Hulzebosch A, Bovenhuis H. Genetic and environmental variation in bovine milk infrared spectra. J Dairy Sci. 2016;99:6793-6803 pubmed publisher
    ..20 to 0.60. The diacylglycerol O-acyltransferase 1 (DGAT1), stearoyl-CoA desaturase (SCD1), ?-casein (CSN3), and ?-lactoglobulin (LGB) polymorphisms are known to have a large effect on milk composition, and therefore we ..
  35. Kapelari B, Bech Otschir D, Hegerl R, Schade R, Dumdey R, Dubiel W. Electron microscopy and subunit-subunit interaction studies reveal a first architecture of COP9 signalosome. J Mol Biol. 2000;300:1169-78 pubmed
    ..Although substrate phosphorylation by COP9 signalosome is significantly decreased by lambda protein phosphatase treatment, "autophosphorylation" is increased. ..
  36. Füzesi Levi M, Ben Nissan G, Bianchi E, Zhou H, Deery M, Lilley K, et al. Dynamic regulation of the COP9 signalosome in response to DNA damage. Mol Cell Biol. 2014;34:1066-76 pubmed publisher
    ..of the CSN complex into the nucleus was seen, accompanied by upregulation of specific phosphorylations within CSN1, CSN3, and CSN8...
  37. Petersen H, Hilpert J, Militz D, Zandler V, Jacobsen C, Roebroek A, et al. Functional interaction of megalin with the megalinbinding protein (MegBP), a novel tetratrico peptide repeat-containing adaptor molecule. J Cell Sci. 2003;116:453-61 pubmed
    ..These finding suggest a model whereby megalin directly participates in transcriptional regulation through controlled sequestration or release of transcription factors via MegBP. ..
  38. Oh W, Lee E, Sung Y, Yang M, Ghim J, Lee H, et al. Jab1 induces the cytoplasmic localization and degradation of p53 in coordination with Hdm2. J Biol Chem. 2006;281:17457-65 pubmed
    ..Our studies implicate that Jab1 is required to remove post-translationally modified p53 and provide a novel target for p53-related cancer therapies. ..
  39. Rozen S, Füzesi Levi M, Ben Nissan G, Mizrachi L, Gabashvili A, Levin Y, et al. CSNAP Is a Stoichiometric Subunit of the COP9 Signalosome. Cell Rep. 2015;13:585-598 pubmed publisher
    ..We show that CSNAP binds CSN3, CSN5, and CSN6, and its incorporation into the CSN complex is mediated through the C-terminal region involving ..
  40. Xiong Y, Wu S, Du Q, Wang A, Wang Z. Integrated analysis of gene expression and genomic aberration data in osteosarcoma (OS). Cancer Gene Ther. 2015;22:524-9 pubmed publisher
    ..PPI network analysis showed that CCT3, COPS3 and WWP1 were the significant hub proteins...
  41. Stotland A, Pruitt L, Webster P, Wolkowicz R. Purification of the COP9 signalosome complex and binding partners from human T cells. OMICS. 2012;16:312-9 pubmed publisher
    ..This proteomic-based approach can broaden our understanding of the functions of the CSN in contexts such as viral-host interactions or immune activation in their natural milieu. ..
  42. Pisano A, Ceglia S, Palmieri C, Vecchio E, Fiume G, De Laurentiis A, et al. CRL3IBTK Regulates the Tumor Suppressor Pdcd4 through Ubiquitylation Coupled to Proteasomal Degradation. J Biol Chem. 2015;290:13958-71 pubmed publisher
    ..By characterizing CRL3(IBTK) as a novel ubiquitin ligase, this study provides new insights into regulatory mechanisms of cellular pathways, such as the Pdcd4-dependent translation of mRNAs. ..
  43. Enchev R, Schreiber A, Beuron F, Morris E. Structural insights into the COP9 signalosome and its common architecture with the 26S proteasome lid and eIF3. Structure. 2010;18:518-27 pubmed publisher
    ..We compare the structure of CSN with its homologous complexes, the 26S proteasome lid and eIF3, and propose a conserved architecture implying similar assembly pathways and/or conserved substrate interaction modes. ..
  44. Ahmad T, Atkulwar A, Farah S, Singh V, Baig M. A new allele of the kappa-casein gene in local zebu cattle breeds. J Dairy Res. 2017;:1-4 pubmed publisher
    ..By using the re-sequencing technology, we sequenced 403 bp of the exon IV CSN3 allele and inferred its haplotypes...
  45. Hong X, Xu L, Li X, Zhai Z, Shu H. CSN3 interacts with IKKgamma and inhibits TNF- but not IL-1-induced NF-kappaB activation. FEBS Lett. 2001;499:133-6 pubmed
    ..These screenings identified CSN3, a component of the COP9 signalsome, as a protein specifically interacting with IKKgamma...
  46. Neuss H, Huang X, Hetfeld B, Deva R, Henklein P, Nigam S, et al. The ubiquitin- and proteasome-dependent degradation of COX-2 is regulated by the COP9 signalosome and differentially influenced by coxibs. J Mol Med (Berl). 2007;85:961-70 pubmed
    ..Addition of valdecoxib also stimulates COX-2 degradation in HeLa cells. We therefore conclude that valdecoxib specifically interacts with COX-2 and induces a conformation accessible for ubiquitination and degradation. ..
  47. Chih D, Park D, Gross M, Idos G, Vuong P, Hirama T, et al. Protein partners of C/EBPepsilon. Exp Hematol. 2004;32:1173-81 pubmed
    ..Our results suggest heterodimeric partners of C/EBPepsilon modulate the function of C/EBPepsilon in mediating gene transcription during myelopoiesis. ..
  48. Lee J, Yi L, Li J, Schweitzer K, Borgmann M, Naumann M, et al. Crystal structure and versatile functional roles of the COP9 signalosome subunit 1. Proc Natl Acad Sci U S A. 2013;110:11845-50 pubmed publisher
    ..Therefore, the CSN complex uses multiple mechanisms to hinder NF-?B activation, a principle likely to hold true for its regulation of many other targets and pathways...
  49. McMichael G, Girirajan S, Moreno De Luca A, Gecz J, Shard C, Nguyen L, et al. Rare copy number variation in cerebral palsy. Eur J Hum Genet. 2014;22:40-5 pubmed publisher
    ..2-p12.1, a 234-kb duplication of 10q26.13, and a 4-kb exonic deletion of COPS3. The inheritance was unknown for three CNVs: a 157-bp exonic deletion of ACOX1, a 693-kb duplication of 17q25...
  50. Bianchi E, Denti S, Granata A, Bossi G, Geginat J, Villa A, et al. Integrin LFA-1 interacts with the transcriptional co-activator JAB1 to modulate AP-1 activity. Nature. 2000;404:617-21 pubmed
    ..We suggest that signalling through the LFA-1 integrin may affect c-Jun-driven transcription by regulating JAB1 nuclear localization. This represents a new pathway for integrin-dependent modulation of gene expression. ..
  51. Serino G, Su H, Peng Z, Tsuge T, Wei N, Gu H, et al. Characterization of the last subunit of the Arabidopsis COP9 signalosome: implications for the overall structure and origin of the complex. Plant Cell. 2003;15:719-31 pubmed
    ..Comparative analyses of the subunit interaction of CSN revealed a set of conserved subunit contacts and resulted in a model of CSN subunit topology, some aspects of which were substantiated by in vivo cross-link tests. ..
  52. Pick E, Golan A, Zimbler J, Guo L, Sharaby Y, Tsuge T, et al. The minimal deneddylase core of the COP9 signalosome excludes the Csn6 MPN- domain. PLoS ONE. 2012;7:e43980 pubmed publisher
    ..We propose that the budding yeast Csi1 is a functional equivalent of the canonical Csn6, and thus the composition of the CSN across phyla is more conserved than hitherto appreciated. ..
  53. Both J, Wu T, Bras J, Schaap G, Baas F, Hulsebos T. Identification of novel candidate oncogenes in chromosome region 17p11.2-p12 in human osteosarcoma. PLoS ONE. 2012;7:e30907 pubmed publisher
    ..Chromosome region 17p11.2-p12 is amplified in about 25% of cases. In previous studies, COPS3 and PMP22 have been identified as candidate oncogenes in this region...
  54. Wolf D, Zhou C, Wee S. The COP9 signalosome: an assembly and maintenance platform for cullin ubiquitin ligases?. Nat Cell Biol. 2003;5:1029-33 pubmed
    ..This apparent paradox can be resolved in a model that proposes CSN-mediated cullin inhibition is a prerequisite for the proper assembly and maintenance of active cullin ubiquitin ligase complexes. ..
  55. Hrecka K, Gierszewska M, Srivastava S, Kozaczkiewicz L, Swanson S, Florens L, et al. Lentiviral Vpr usurps Cul4-DDB1[VprBP] E3 ubiquitin ligase to modulate cell cycle. Proc Natl Acad Sci U S A. 2007;104:11778-83 pubmed publisher
  56. Asare Y, Shagdarsuren E, Schmid J, Tilstam P, Grommes J, El Bounkari O, et al. Endothelial CSN5 impairs NF-?B activation and monocyte adhesion to endothelial cells and is highly expressed in human atherosclerotic lesions. Thromb Haemost. 2013;110:141-52 pubmed publisher
    ..In conclusion, endothelial CSN5 attenuates NF-?B-dependent pro-inflammatory gene expression and monocyte arrest on stimulated endothelial cells in vitro, suggesting that CSN5 might serve as a negative regulator of atherogenesis. ..
  57. Potocki L, Chen K, Lupski J. Subunit 3 of the COP9 signal transduction complex is conserved from plants to humans and maps within the smith-magenis syndrome critical region in 17p11.2. Genomics. 1999;57:180-2 pubmed
  58. NAJOR N, Fitz G, Koetsier J, Godsel L, Albrecht L, Harmon R, et al. Epidermal Growth Factor Receptor neddylation is regulated by a desmosomal-COP9 (Constitutive Photomorphogenesis 9) signalosome complex. elife. 2017;6: pubmed publisher
    ..desmosomes assist the de-neddylating COP9 signalosome (CSN) in attenuating EGFR through an association between the Cops3 subunit of the CSN and desmosomal components, Desmoglein1 (Dsg1) and Desmoplakin (Dp), to promote epidermal ..
  59. Huang X, Ordemann J, Pratschke J, Dubiel W. Overexpression of COP9 signalosome subunits, CSN7A and CSN7B, exerts different effects on adipogenic differentiation. FEBS Open Bio. 2016;6:1102-1112 pubmed
  60. Yu Y, Tang Z, Pan Q, Chen X, Liu X, Zang G. Inhibition of Csn3 expression induces growth arrest and apoptosis of hepatocellular carcinoma cells. Cancer Chemother Pharmacol. 2012;69:1173-80 pubmed publisher
    b>Csn3 (or CSN3) encodes the third subunit of an eight-subunit complex, the COP9 signalosome (CSN), which acts as a protein kinase and a deneddylase in mammalian cells...
  61. Latini P, Frontini M, Caputo M, Gregan J, Cipak L, Filippi S, et al. CSA and CSB proteins interact with p53 and regulate its Mdm2-dependent ubiquitination. Cell Cycle. 2011;10:3719-30 pubmed publisher
    ..The deregulation of p53, in absence of either of the CS proteins, can potentially explain the early onset degeneration of tissues and organs observed in CS patients. ..
  62. Seeger M, Kraft R, Ferrell K, Bech Otschir D, Dumdey R, Schade R, et al. A novel protein complex involved in signal transduction possessing similarities to 26S proteasome subunits. FASEB J. 1998;12:469-78 pubmed
    ..Three subunits of the new complex--Sgn3, Sgn5/JAB1, and Sgn6--exhibit sequence similarities to regulatory components of the 26S proteasome, which could ..
  63. Hoareau Alves K, Bochard V, Rety S, Jalinot P. Association of the mammalian proto-oncoprotein Int-6 with the three protein complexes eIF3, COP9 signalosome and 26S proteasome. FEBS Lett. 2002;527:15-21 pubmed
    ..screen with Int-6 as bait, we have isolated subunits belonging to all three complexes, namely eIF3-p110, Rpt4, CSN3 and CSN6...
  64. Zhang M, Zhao S, Wang S, Luo C, Gao H, Zheng N, et al. d-Glucose and amino acid deficiency inhibits casein synthesis through JAK2/STAT5 and AMPK/mTOR signaling pathways in mammary epithelial cells of dairy cows. J Dairy Sci. 2018;101:1737-1746 pubmed publisher
    ..The expression levels of ?-casein and ?-casein (encoded by CSN2 and CSN3) were measured by quantitative real-time PCR and Western blotting...
  65. Orel L, Neumeier H, Hochrainer K, Binder B, Schmid J. Crosstalk between the NF-kappaB activating IKK-complex and the CSN signalosome. J Cell Mol Med. 2010;14:1555-68 pubmed publisher
    ..Upon activation of cells with tumour necrosis factor-alpha, the CSN complex dissociates from IKK's allowing full and rapid activation of the NF-kappaB pathway by the concerted action of interacting protein complexes. ..
  66. Zitouni M, Viens P, Ghinet M, Brzezinski R. Diversity of family GH46 chitosanases in Kitasatospora setae KM-6054. Appl Microbiol Biotechnol. 2017;101:7877-7888 pubmed publisher
    ..Sequence analysis showed that Csn1 and Csn2H were canonical GH46 chitosanases, while Csn3 resembled chitosanases from bacilli...
  67. Sanchez M, Govignon Gion A, Croiseau P, Fritz S, Hozé C, Miranda G, et al. Within-breed and multi-breed GWAS on imputed whole-genome sequence variants reveal candidate mutations affecting milk protein composition in dairy cattle. Genet Sel Evol. 2017;49:68 pubmed publisher
    ..including those with previously described effects on milk composition (SLC37A1, MGST1, ABCG2, CSN1S1, CSN2, CSN1S2, CSN3, PAEP, DGAT1, AGPAT6) and those with effects reported for the first time here (ALPL, ANKH, PICALM)...
  68. Zepeda Batista J, Saavedra Jiménez L, Ruíz Flores A, Núñez Domínguez R, Ramírez Valverde R. Potential influence of ?-casein and ?-lactoglobulin genes in genetic association studies of milk quality traits. Asian-Australas J Anim Sci. 2017;30:1684-1688 pubmed publisher
    ..of published information on genetic association studies, a meta-analysis was conducted to determine the influence of the genes ?-casein (CSN3) and ?-lactoglobulin (LGB) on milk yield traits in Holstein, Jersey, Brown Swiss, and Fleckvieh.
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    ..01) decreased as well as other milk protein coding genes, such as CSN1S1, CSN1S2, CSN2, CSN3 and LALBA (p < 0.05). As expected, BLG protein had been abolished in the milk of the BLG knock-out goat...
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    ..We propose possible functional consequences of these novel Raf interactions. ..
  71. Neamt R, Saplacan G, Acatincai S, Cziszter L, Gavojdian D, Ilie D. The influence of CSN3 and LGB polymorphisms on milk production and chemical composition in Romanian Simmental cattle. Acta Biochim Pol. 2017;64:493-497 pubmed publisher
    The aim of this study was to assess the influence of genotypes from the CSN3 and LGB loci on milk production and chemical composition in Romanian Simmental cattle (n=114). For the CSN3 locus a significantly higher frequency (P≤0...
  72. McCall C, Miliani de Marval P, Chastain P, Jackson S, He Y, Kotake Y, et al. Human immunodeficiency virus type 1 Vpr-binding protein VprBP, a WD40 protein associated with the DDB1-CUL4 E3 ubiquitin ligase, is essential for DNA replication and embryonic development. Mol Cell Biol. 2008;28:5621-33 pubmed publisher
    ..Our studies identify a previously unknown function of VprBP in S-phase progression and suggest the possibility that HIV-1 Vpr may divert an ongoing chromosomal replication activity to facilitate viral replication. ..
  73. Kulaksiz G, Reardon J, Sancar A. Xeroderma pigmentosum complementation group E protein (XPE/DDB2): purification of various complexes of XPE and analyses of their damaged DNA binding and putative DNA repair properties. Mol Cell Biol. 2005;25:9784-92 pubmed
  74. Yoneda Kato N, Tomoda K, Umehara M, Arata Y, Kato J. Myeloid leukemia factor 1 regulates p53 by suppressing COP1 via COP9 signalosome subunit 3. EMBO J. 2005;24:1739-49 pubmed
    ..This action requires a novel binding partner, subunit 3 of the COP9 signalosome (CSN3)...
  75. van Dartel M, Hulsebos T. Amplification and overexpression of genes in 17p11.2 ~ p12 in osteosarcoma. Cancer Genet Cytogenet. 2004;153:77-80 pubmed
    ..Genes PMP22 and COPS3 and three expressed sequence tags from within 17p11...
  76. Huang X, Ordemann J, Muller J, Dubiel W. The COP9 signalosome, cullin 3 and Keap1 supercomplex regulates CHOP stability and adipogenesis. Biol Open. 2012;1:705-10 pubmed publisher
    ..We conclude that CHOP stability is controlled by a CSN-CRL3(Keap1) complex, which is crucial for adipogenesis. Our data show that CHOP is a distinguished target for pharmacological intervention of obesity. ..
  77. Taye M, Lee W, Jeon S, Yoon J, Dessie T, Hanotte O, et al. Exploring evidence of positive selection signatures in cattle breeds selected for different traits. Mamm Genome. 2017;28:528-541 pubmed publisher
    ..Moreover, significant breed-specific missense variants were identified in CSN3, PAPPA2 (Holstein), C1orf116 (Hanwoo), and COMMD1 (N'Dama) genes...