Genomes and Genes
Gene Symbol: COPS6
Description: COP9 signalosome subunit 6
Alias: CSN6, MOV34-34KD, COP9 signalosome complex subunit 6, COP9 constitutive photomorphogenic homolog subunit 6, H_NH0506M12.12, JAB1-containing signalosome subunit 6, MOV34 homolog, 34 kD, SGN6, hVIP, vpr-interacting protein
- Birol M, Echalier A. Structure and function of MPN (Mpr1/Pad1 N-terminal) domain-containing proteins. Curr Protein Pept Sci. 2014;15:504-17 pubmed..Constitutive photomorphogenesis 9) signalosome complexes, including the MPN subunits, POH1 and Mov34, CSN5 and CSN6, respectively...
- Chen J, Shin J, Zhao R, Phan L, Wang H, Xue Y, et al. CSN6 drives carcinogenesis by positively regulating Myc stability. Nat Commun. 2014;5:5384 pubmed publisher..Here we show that Myc is a target of the CSN subunit 6 (CSN6)-Cullin signalling axis and that CSN6 is a positive regulator of Myc...
- 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...
- 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..RING domain is crucial for deneddylation, and works in part through conformational changes involving insert-2 of Csn6. Nedd8 deconjugation and re-engagement of the active site zinc by the autoinhibitory Csn5 glutamate-104 diminish ..
- Tan S, Liu F, Pan X, Zang Y, Jin F, Zu W, et al. CSN6, a subunit of the COP9 signalosome, is involved in early response to iron deficiency in Oryza sativa. Sci Rep. 2016;6:25485 pubmed publisher..b>CSN6 expression is rapidly down-regulated during Fe depletion, contributing to reduced CSN activity, as judged by CSN5 ..
- Rozen S, FÃ¼zesi 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 conserved aromatic ..
- Hou J, Deng Q, Zhou J, Zou J, Zhang Y, Tan P, et al. CSN6 controls the proliferation and metastasis of glioblastoma by CHIP-mediated degradation of EGFR. Oncogene. 2017;36:1134-1144 pubmed publisherb>CSN6, a critical subunit of the constitutive photomorphogenesis 9 (COP9) signalosome (CSN), has received attention as a regulator of the degradation of cancer-related proteins such as p53, c-myc and c-Jun, through the ubiquitin-proteasome ..
- Ramanathan M, Curley E, Su M, Chambers J, Weiner D. Carboxyl terminus of hVIP/mov34 is critical for HIV-1-Vpr interaction and glucocorticoid-mediated signaling. J Biol Chem. 2002;277:47854-60 pubmed..hVIP/mov34 (human Vpr Interacting Protein) is one of these identified Vpr ligands...
- Shi J, Feng Y, Goulet A, Vaillancourt R, Sachs N, Hershey J, et al. The p34cdc2-related cyclin-dependent kinase 11 interacts with the p47 subunit of eukaryotic initiation factor 3 during apoptosis. J Biol Chem. 2003;278:5062-71 pubmed..Stable expression of CDK11(p46) in vivo inhibited the synthesis of a transfected luciferase reporter protein and overall cellular protein synthesis. These data provide insight into the cellular function of CDK11 during apoptosis. ..
- 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. ..
- Poon B, Jowett J, Stewart S, Armstrong R, Rishton G, Chen I. Human immunodeficiency virus type 1 vpr gene induces phenotypic effects similar to those of the DNA alkylating agent, nitrogen mustard. J Virol. 1997;71:3961-71 pubmed..These results are consistent with the hypothesis that Vpr induces G2 arrest through pathways that are similar to those utilized by DNA-damaging agents. ..
- Birol M, Enchev R, Padilla A, Stengel F, Aebersold R, Betzi S, et al. Structural and biochemical characterization of the Cop9 signalosome CSN5/CSN6 heterodimer. PLoS ONE. 2014;9:e105688 pubmed publisher..The association of CSN5 and CSN6 MPN (for Mpr1/Pad1 N-terminal) domains activates its isopeptidase activity...
- Ma X, Xu M, Jiang T. Crystal structure of the human CSN6 MPN domain. Biochem Biophys Res Commun. 2014;453:25-30 pubmed publisher..CSN5 and CSN6 are the only two MPN (Mpr1-Pad1-N-terminal) domain-containing subunits in the complex...
- Fang L, Lu W, Choi H, Yeung S, Tung J, Hsiao C, et al. ERK2-Dependent Phosphorylation of CSN6 Is Critical in Colorectal Cancer Development. Cancer Cell. 2015;28:183-97 pubmed publisherBiomarkers for predicting prognosis are critical to treating colorectal cancer (CRC) patients. We found that CSN6, a subunit of COP9 signalosome, is overexpressed in CRC samples and that CSN6 overexpression is correlated with poor patient ..
- Hetfeld B, Peth A, Sun X, Henklein P, Cohen G, Dubiel W. The COP9 signalosome-mediated deneddylation is stimulated by caspases during apoptosis. Apoptosis. 2008;13:187-95 pubmed..However, little is known about the CSN during apoptosis. We demonstrate in vitro and in vivo that CSN6 is cleaved most effectively by caspase 3 at D23 after 2-3 h of apoptosis induced by anti-Fas-Ab or etoposide...
- 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. ..
- Chen B, Zhao R, Su C, Linan M, Tseng C, Phan L, et al. CDK inhibitor p57 (Kip2) is negatively regulated by COP9 signalosome subunit 6. Cell Cycle. 2012;11:4633-41 pubmed publisherSubunit 6 of the COP9 signalosome complex, CSN6, is known to be critical to the regulation of the MDM2-p53 axis for cell proliferation and anti-apoptosis, but its many targets remain unclear...
- Shin J, Phan L, Chen J, Lu Z, Lee M. CSN6 positively regulates c-Jun in a MEKK1-dependent manner. Cell Cycle. 2015;14:3079-87 pubmed publisher..The COP9 signalosome subunit 6 (CSN6) plays a critical role in ubiquitin-mediated protein degradation...
- da Silva Correia J, Miranda Y, Leonard N, Ulevitch R. The subunit CSN6 of the COP9 signalosome is cleaved during apoptosis. J Biol Chem. 2007;282:12557-65 pubmed..Moreover, we observed that activation of the Nod1 apoptotic pathway leads to specific cleavage of the subunit CSN6. This cleavage is concomitant with caspase processing and generates a short amino-terminal peptide of 3 kDa...
- Zhao L, Mukherjee S, Narayan O. Biochemical mechanism of HIV-I Vpr function. Specific interaction with a cellular protein. J Biol Chem. 1994;269:15577-82 pubmed..These results suggest that RIP may be involved in Vpr function. ..
- Burger Kentischer A, Finkelmeier D, Thiele M, Schmucker J, Geiger G, Tovar G, et al. Binding of JAB1/CSN5 to MIF is mediated by the MPN domain but is independent of the JAMM motif. FEBS Lett. 2005;579:1693-701 pubmed..Finally, endogenous CoIP of MIF-CSN6 complexes from mammalian cells demonstrated that MPN is responsible for MIF-JAB1 binding in vivo, and, as CSN6 does ..
- 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. ..
- 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. ..
- Ramanathan M, Ayyavoo V, Weiner D. Choice of expression vector alters the localization of a human cellular protein. DNA Cell Biol. 2001;20:101-5 pubmed..In this report, we demonstrate that the mere expression of a cellular protein, hVIP/mov34, which we earlier identified as a cellular HIV-1 Vpr ligand, in two different vectors clearly altered its ..
- Re F, Braaten D, Franke E, Luban J. Human immunodeficiency virus type 1 Vpr arrests the cell cycle in G2 by inhibiting the activation of p34cdc2-cyclin B. J Virol. 1995;69:6859-64 pubmed..These studies demonstrate that HIV-1 vpr has profound effects on the cellular factors which control entry into mitosis and indicate vpr's potential contribution to the cellular pathology associated with HIV-1 infection. ..
- 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..Taken together, our results suggest that the specific spatiotemporal composition of the CSN is highly controlled, enabling the complex to rapidly adapt and respond to DNA damage. ..
- 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. ..
- 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. ..
- Choi H, Guma S, Fang L, Phan L, Ivan C, Baggerly K, et al. Regulating the stability and localization of CDK inhibitor p27(Kip1) via CSN6-COP1 axis. Cell Cycle. 2015;14:2265-73 pubmed publisherThe COP9 signalosome subunit 6 (CSN6), which is involved in ubiquitin-mediated protein degradation, is overexpressed in many types of cancer...
- Jowett J, Planelles V, Poon B, Shah N, Chen M, Chen I. The human immunodeficiency virus type 1 vpr gene arrests infected T cells in the G2 + M phase of the cell cycle. J Virol. 1995;69:6304-13 pubmed..Cell cycle arrest induced by Vpr correlates with an increase in the hyperphosphorylated (inactive) form of the cyclin-dependent serine/threonine kinase CDC2, consistent with an arrest of cells at the boundary of G2 and M. ..
- Mittmeyer H. [Distribution pattern of rigor mortis in various joint regions]. Beitr Gerichtl Med. 1975;33:85-96 pubmed
- Zhang H, Zhong A, Sun J, Chen M, Xie S, Zheng H, et al. COPS5 inhibition arrests the proliferation and growth of serous ovarian cancer cells via the elevation of p27 level. Biochem Biophys Res Commun. 2017;493:85-93 pubmed publisher..the cells were stuck at S-phase accompanied with an elevation of nucleus p27 expression after knocking down COPS6 or blocking COPS5 by CSN5i-3...
- 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. ..
- Mahalingam S, Ayyavoo V, Patel M, Kieber Emmons T, Kao G, Muschel R, et al. HIV-1 Vpr interacts with a human 34-kDa mov34 homologue, a cellular factor linked to the G2/M phase transition of the mammalian cell cycle. Proc Natl Acad Sci U S A. 1998;95:3419-24 pubmed..We have cloned a candidate Vpr ligand, termed human Vpr interacting protein (hVIP/MOV34), by using a yeast two-hybrid assay...
- Asano K, Vornlocher H, Richter Cook N, Merrick W, Hinnebusch A, Hershey J. Structure of cDNAs encoding human eukaryotic initiation factor 3 subunits. Possible roles in RNA binding and macromolecular assembly. J Biol Chem. 1997;272:27042-52 pubmed..The subunit composition of eIF3 appears to be highly conserved in Drosophila melanogaster, C. elegans, and Arabidopsis thaliana, whereas only 5 homologs of the 10 subunits of mammalian eIF3 are encoded in S. cerevisiae. ..
- Muthumani K, Choo A, PremKumar A, Hwang D, Thieu K, Desai B, et al. Human immunodeficiency virus type 1 (HIV-1) Vpr-regulated cell death: insights into mechanism. Cell Death Differ. 2005;12 Suppl 1:962-70 pubmed..Further, we also discuss caveats and future directions for investigation of the interesting biology of this HIV accessory gene. ..
- Gastaldello S, Callegari S, Coppotelli G, Hildebrand S, Song M, Masucci M. Herpes virus deneddylases interrupt the cullin-RING ligase neddylation cycle by inhibiting the binding of CAND1. J Mol Cell Biol. 2012;4:242-51 pubmed publisher..These findings illustrate a new strategy for viral modulation of CRL activity where the combined effects of cullin deneddylation and their targeting for proteasomal degradation drive stable inactivation of the ligases...
- Gao S, Fang L, Phan L, Qdaisat A, Yeung S, Lee M. COP9 signalosome subunit 6 (CSN6) regulates E6AP/UBE3A in cervical cancer. Oncotarget. 2015;6:28026-41 pubmed publisher..The COP9 signalosome subunit 6 (CSN6) is involved in ubiquitin-mediated protein degradation...
- 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
- 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..For instance, in plant cells, isoforms have been identified for the MPN-domain subunits CSN5 (CSN5A and CSN5B) and CSN6 (CSN6A and CSN6B) which form four distinct CSN variants...
- He J, Choe S, Walker R, Di Marzio P, Morgan D, Landau N. Human immunodeficiency virus type 1 viral protein R (Vpr) arrests cells in the G2 phase of the cell cycle by inhibiting p34cdc2 activity. J Virol. 1995;69:6705-11 pubmed..In vivo, Vpr might, by preventing p34cdc2 activation, delay or prevent apoptosis of infected cells. This would increase the amount of virus each infected cell produced. ..
- Choi H, Gully C, Su C, Velazquez Torres G, Chou P, Tseng C, et al. COP9 signalosome subunit 6 stabilizes COP1, which functions as an E3 ubiquitin ligase for 14-3-3?. Oncogene. 2011;30:4791-801 pubmed publisher..We show for the first time that COP9 signalosome subunit 6 (CSN6) associates with COP1 and is involved in 14-3-3? ubiquitin-mediated degradation...
- 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..with Int-6 as bait, we have isolated subunits belonging to all three complexes, namely eIF3-p110, Rpt4, CSN3 and CSN6. The results of transient expression experiments in COS7 cells confirmed the interaction of Int-6 with Rpt4, CSN3 ..
- Hrimech M, Yao X, Branton P, Cohen E. Human immunodeficiency virus type 1 Vpr-mediated G(2) cell cycle arrest: Vpr interferes with cell cycle signaling cascades by interacting with the B subunit of serine/threonine protein phosphatase 2A. EMBO J. 2002;21:3918 pubmed
- 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 indicate the existence ..
- 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. ..
- Yang L, Liu Y, Wang M, Qian Y, Dong X, Gu H, et al. Quercetin-induced apoptosis of HT-29 colon cancer cells via inhibition of the Akt-CSN6-Myc signaling axis. Mol Med Rep. 2016;14:4559-4566 pubmed publisher..b>CSN6 may promote carcinogenesis by positively regulating v?myc avian myelocytomatosis viral oncogene homolog (Myc) and ..
- Elder R, Yu M, Chen M, Edelson S, Zhao Y. Cell cycle G2 arrest induced by HIV-1 Vpr in fission yeast (Schizosaccharomyces pombe) is independent of cell death and early genes in the DNA damage checkpoint. Virus Res. 2000;68:161-73 pubmed..This conclusion was further supported by the observation that mutations in Vpr, which have lost their ability to induce G2 arrest, retained the ability to kill cells. ..
- 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..The core of the subcomplex is based on a stable heterotrimeric association of CSN7, CSN4, and CSN6, requiring coexpression in a bacterial reconstitution system...
- 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. ..
- 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. ..
- Di Marzio P, Choe S, Ebright M, Knoblauch R, Landau N. Mutational analysis of cell cycle arrest, nuclear localization and virion packaging of human immunodeficiency virus type 1 Vpr. J Virol. 1995;69:7909-16 pubmed..We speculate that Vpr has two sites for interaction with cellular factors: one in the alpha-helical region that specifies nuclear localization and one in the carboxy-terminal domain that is required for Cdc2 inhibition. ..