COPS4

Summary

Gene Symbol: COPS4
Description: COP9 signalosome subunit 4
Alias: CSN4, SGN4, COP9 signalosome complex subunit 4, COP9 constitutive photomorphogenic homolog subunit 4, COP9 constitutive photomorphogenic-like protein subunit 4, JAB1-containing signalosome subunit 4, signalosome subunit 4, testis tissue sperm-binding protein Li 42a
Species: human
Products:     COPS4

Top Publications

  1. Peyrl A, Weitzdoerfer R, Gulesserian T, Fountoulakis M, Lubec G. Aberrant expression of signaling-related proteins 14-3-3 gamma and RACK1 in fetal Down syndrome brain (trisomy 21). Electrophoresis. 2002;23:152-7 pubmed
  2. 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
  3. 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.
  4. 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. ..
  5. 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
    ..we are able to build a comprehensive interaction map that shows two symmetrical modules, Csn1/2/3/8 and Csn4/5/6/7, connected by interactions between Csn1-Csn6...
  6. 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. ..
  7. Pan L, Wang S, Lu T, Weng C, Song X, Park J, et al. Protein competition switches the function of COP9 from self-renewal to differentiation. Nature. 2014;514:233-6 pubmed publisher
    ..the COP9 complex is required intrinsically for GSC self-renewal, whereas other Csn proteins, with the exception of Csn4, were also required for GSC progeny differentiation...
  8. Păcurar D, Pacurar M, Lakehal A, Pacurar A, Ranjan A, Bellini C. The Arabidopsis Cop9 signalosome subunit 4 (CNS4) is involved in adventitious root formation. Sci Rep. 2017;7:628 pubmed publisher
    ..Here we report the identification and characterization of a viable allele of the Arabidopsis COP9 signalosome subunit 4 (CSN4)...
  9. Mosadeghi R, Reichermeier K, Winkler M, Schreiber A, Reitsma J, Zhang Y, et al. Structural and kinetic analysis of the COP9-Signalosome activation and the cullin-RING ubiquitin ligase deneddylation cycle. elife. 2016;5: pubmed publisher
    ..large conformational changes upon binding, with important roles played by the N-terminal domains of Csn2 and Csn4 and the RING domain of Rbx1 in enabling formation of a high affinity, fully active complex...

More Information

Publications40

  1. Zarrei M, Merico D, Kellam B, Engchuan W, Scriver T, Jokhan R, et al. A de novo deletion in a boy with cerebral palsy suggests a refined critical region for the 4q21.22 microdeletion syndrome. Am J Med Genet A. 2017;173:1287-1293 pubmed publisher
    ..2?Mb critical region encompassing ten protein-coding genes, of which six (PRKG2, RASGEF1B, HNRNPDL, HNRNPD, LIN54, COPS4) have a significantly low number of truncating loss-of-function mutations...
  2. 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...
  3. Bhansali M, Shemshedini L. COP9 subunits 4 and 5 target soluble guanylyl cyclase ?1 and p53 in prostate cancer cells. Mol Endocrinol. 2014;28:834-45 pubmed publisher
    ..We identified the COP9 signalosome subunit 4 (CSN4) as a novel interacting partner for sGC?1...
  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. 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. ..
  6. Naumann M, Bech Otschir D, Huang X, Ferrell K, Dubiel W. COP9 signalosome-directed c-Jun activation/stabilization is independent of JNK. J Biol Chem. 1999;274:35297-300 pubmed
    ..The c-Jun activation caused by Sgn2 overexpression is independent of JNK and mitogen-activated protein kinase kinase 4. The data demonstrate the existence of a novel COP9 signalosome-directed c-Jun activation pathway. ..
  7. 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. ..
  8. Cohen H, Azriel A, Cohen T, Meraro D, Hashmueli S, Bech Otschir D, et al. Interaction between interferon consensus sequence-binding protein and COP9/signalosome subunit CSN2 (Trip15). A possible link between interferon regulatory factor signaling and the COP9/signalosome. J Biol Chem. 2000;275:39081-9 pubmed
    ..This suggests that the CSN has a role in integrating incoming signals that affect the transcriptional activity of ICSBP. ..
  9. 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
  10. 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. ..
  11. 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
    ..Curcumin treatment results in elevated amounts of c-Jun-Ub conjugates. We conclude that CK2 and PKD are recruited by CSN in order to regulate Ub conjugate formation. ..
  12. 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. ..
  13. 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. ..
  14. 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
    ..Considering the putative role of the complex in signal transduction and its widespread occurrence, we suggest the name JAB1-containing signalosome. ..
  15. Kotiguda G, Weinberg D, Dessau M, Salvi C, Serino G, Chamovitz D, et al. The organization of a CSN5-containing subcomplex of the COP9 signalosome. J Biol Chem. 2012;287:42031-41 pubmed publisher
    ..step to understanding the structure and assembly of a CSN5-containing subcomplex of the CSN, we reconstituted a CSN4-5-6-7 subcomplex...
  16. Wang W, Huang J, Wang X, Yuan J, Li X, Feng L, et al. PTPN14 is required for the density-dependent control of YAP1. Genes Dev. 2012;26:1959-71 pubmed publisher
    ..Collectively, these data suggest that PTPN14 acts to suppress cell proliferation by promoting cell density-dependent cytoplasmic translocation of YAP1. ..
  17. Shibata E, Abbas T, Huang X, Wohlschlegel J, Dutta A. Selective ubiquitylation of p21 and Cdt1 by UBCH8 and UBE2G ubiquitin-conjugating enzymes via the CRL4Cdt2 ubiquitin ligase complex. Mol Cell Biol. 2011;31:3136-45 pubmed publisher
    ..These findings identify the UBCs required for the activity of CRL4(Cdt2) on multiple substrates and demonstrate that different UBCs are involved in the selective ubiquitylation of different substrates by the same E3 complex. ..
  18. 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. ..
  19. 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. ..
  20. 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
    ..Taken together these results show that the Int-6 protein can bind the three complexes with various efficiencies, possibly exerting a regulatory activity in both protein translation and degradation. ..
  21. Zheng W, Dong X, Yin R, Xu F, Ning H, Zhang M, et al. EDAG positively regulates erythroid differentiation and modifies GATA1 acetylation through recruiting p300. Stem Cells. 2014;32:2278-89 pubmed publisher
    ..Microarray analysis suggested that EDAG knockdown selectively inhibits GATA1-activated target genes. These data provide novel insights into EDAG in regulation of erythroid differentiation. ..
  22. 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. ..
  23. 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
    ..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...
  24. 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
  25. 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. ..
  26. Schwechheimer C, Deng X. COP9 signalosome revisited: a novel mediator of protein degradation. Trends Cell Biol. 2001;11:420-6 pubmed
    ..Here, we discuss these recent findings, which add an additional component to the biology of substrate-specific protein degradation. ..
  27. 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. ..
  28. 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. ..
  29. Kolobynina K, Solovyova V, Levay K, Rizvanov A, Slepak V. Emerging roles of the single EF-hand Ca2+ sensor tescalcin in the regulation of gene expression, cell growth and differentiation. J Cell Sci. 2016;129:3533-3540 pubmed
    ..and regulate the activities of the Na+/H+ exchanger NHE1, subunit 4 of the COP9 signalosome (CSN4) and protein kinase glycogen-synthase kinase 3 (GSK3)...
  30. 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. ..
  31. Granata A, Koo S, Haucke V, Schiavo G, Warner T. CSN complex controls the stability of selected synaptic proteins via a torsinA-dependent process. EMBO J. 2011;30:181-93 pubmed publisher
    ..In this study, we identified a novel-binding partner of TA, the subunit 4 (CSN4) of CSN signalosome...