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Showing COPS8 — CSN8 is a alias.

COPS8

COP9 signalosome complex subunit 8 · UniProt Q99627

Length
209 aa
Mass
23.2 kDa
Annotated
2026-06-09
100 papers in source corpus 15 papers cited in narrative 15 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COPS8 (CSN8) is an essential structural subunit of the COP9 signalosome (CSN) whose central function is to maintain holocomplex integrity required for cullin deneddylation and thereby regulation of cullin-RING ubiquitin ligase activity and downstream protein degradation (PMID:21051661, PMID:18706515). Loss of COPS8 destabilizes the other CSN subunits, collapses holocomplex formation, and causes accumulation of neddylated cullins, loss of F-box proteins such as Skp2, and broad dysfunction of the ubiquitin-proteasome system (PMID:21051661, PMID:20689553, PMID:18706515). Within the assembled complex, CSN8 occupies a defined position, interacting with the CSN4-6-7 heterotrimer during subcomplex assembly (PMID:23086934), and a cytoplasmic CRM1-dependent CSN4-8 subcomplex participates in degradation of the cell-cycle inhibitor p27 (PMID:11704659). Through control of cullin-RING ligase activity, COPS8 governs turnover of cell-cycle inhibitors p21 and p27 and is required for antigen-induced T-cell proliferation and G0-to-cell-cycle entry (PMID:17906629, PMID:18706515). In vivo, COPS8 is indispensable for survival and proliferation of cardiomyocytes, hepatocytes, and T cells: cardiomyocyte- and hepatocyte-restricted knockouts produce hyperneddylation of cullins, impaired proteasomal and autophagic protein clearance, and massive cell death (PMID:21051661, PMID:23873473, PMID:20689553). COPS8 also supports autophagosome maturation, in part through control of Rab7 expression (PMID:21986281), promotes cullin-RING ligase-dependent clearance of cytosolic misfolded proteins to protect against cardiac proteotoxicity (PMID:26383969), and suppresses RIPK1-RIPK3-MLKL-dependent cardiomyocyte necroptosis (PMID:32578441). Beyond its core CSN role, COPS8 functions downstream of AhR signaling to drive anti-microbial peptide expression in intestinal epithelium (PMID:34994476) and participates in NF-κB signaling (PMID:22992343, PMID:33261601).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2001 Medium

    Established that CSN8 resides not only in the full signalosome but also in a smaller cytoplasmic CSN4-8 subcomplex linked to degradation of the cell-cycle inhibitor p27, the first functional placement of CSN8 in protein turnover.

    Evidence Glycerol gradient sedimentation, cell fractionation, leptomycin B sensitivity, and ectopic subunit expression with p27 readout

    PMID:11704659

    Open questions at the time
    • Direct catalytic role of CSN8 vs. structural contribution not separated
    • Mechanism linking cytoplasmic export to p27 degradation not resolved
  2. 2007 High

    Showed in vivo that CSN8 is required for CSN holocomplex formation and for antigen-driven T-cell proliferation, linking the complex to transcriptional control of cell-cycle entry via p21Cip1 and G1 cyclins/CDKs.

    Evidence Conditional T-cell-specific Csn8 knockout mice with cell-cycle, proliferation, cytokine, and gene-expression readouts

    PMID:17906629

    Open questions at the time
    • Whether p21 control is direct CRL-mediated or transcriptional was incompletely separated
    • Mechanism of G1 cyclin induction failure not defined
  3. 2008 Medium

    Defined the molecular hierarchy by which CSN8 loss collapses the complex: RNAi destabilized other CSN subunits, increased neddylated cullins, reduced Skp2, and altered turnover of p21 and p27, establishing CSN8 as required for complex integrity and cullin deneddylation.

    Evidence siRNA knockdown in HEK293 cells with western blotting, surrogate substrate assay, and RT-PCR

    PMID:18706515

    Open questions at the time
    • Single-lab study with limited orthogonal validation
    • Distinction between transcriptional and proteolytic effects on p21/p27 not fully resolved
  4. 2010 High

    Demonstrated organismal essentiality: cardiomyocyte- and hepatocyte-restricted Csn8 knockouts impaired holocomplex formation and cullin deneddylation, caused UPS dysfunction, cell death, and proliferation defects, establishing COPS8 as required for postnatal cell survival.

    Evidence Conditional Cre-LoxP knockouts in mouse heart and liver with neddylation blots, surrogate UPS substrate, apoptosis/proliferation assays, and histology

    PMID:20689553 PMID:21051661

    Open questions at the time
    • Cell-death pathway downstream of UPS failure not yet defined
    • Critical CRL substrates driving the phenotype not identified
  5. 2011 High

    Extended CSN8 function to the autophagic-lysosomal pathway, showing it controls autophagosome maturation through Rab7, broadening its role beyond proteasomal degradation.

    Evidence Conditional Csn8 KO hearts with GFP-LC3 imaging, EM, flux assays, and Rab7 rescue/knockdown

    PMID:21986281

    Open questions at the time
    • Mechanism linking CSN to Rab7 expression not defined
    • Whether Rab7 regulation is CRL-dependent unknown
  6. 2012 Medium

    Resolved CSN8's architectural position by reconstituting subcomplexes and showing it docks onto the CSN4-6-7 heterotrimer, clarifying assembly logic of the signalosome.

    Evidence Bacterial co-expression reconstitution, pull-down, size-exclusion chromatography, analytical ultracentrifugation

    PMID:23086934

    Open questions at the time
    • Atomic-resolution structure of CSN8 contacts not determined
    • Full holocomplex assembly with CSN1-3 not reconstituted
  7. 2012 Medium

    Placed COPS8 within GPCR/NF-κB signaling as a miR-146a target downstream of LPA, expanding its role beyond the canonical CSN-CRL axis.

    Evidence miR-146a transfection, luciferase 3'UTR reporter, western blot, NF-κB and cytokine assays in gastric cancer cells

    PMID:22992343

    Open questions at the time
    • Direct mechanism by which COPS8 modulates NF-κB not defined
    • Pathway placement is indirect
  8. 2013 High

    Confirmed in adult hearts that CSN8 is indispensable to both proteasomal and autophagic clearance, ruling out a developmental-only requirement.

    Evidence Temporally controlled conditional Csn8 ablation in adult mice with neddylation blots, surrogate substrate, autophagic flux, histology, echocardiography

    PMID:23873473

    Open questions at the time
    • Relative contribution of proteasomal vs. autophagic failure to necrosis unresolved
  9. 2014 Medium

    Revealed dynamic regulation of CSN8 by stress, with UV-induced phosphorylation and nuclear shuttling of the CSN complex, indicating signal-responsive control of CSN localization.

    Evidence Biochemical fractionation, fluorescence microscopy, and MS-based phosphoproteomics in UV time-course

    PMID:24421388

    Open questions at the time
    • Functional consequence of CSN8 phosphorylation not established
    • Kinase responsible not identified
  10. 2015 High

    Showed COPS8 promotes cullin-RING-ligase-dependent degradation of cytosolic misfolded proteins, defining a protective role against proteotoxicity.

    Evidence CSN8 hypomorphic mice crossed with CryABR120G proteinopathy model plus cardiomyocyte knockdown and ubiquitination assays

    PMID:26383969

    Open questions at the time
    • Specific CRL/E3 ligase mediating misfolded-protein clearance not identified
  11. 2020 High

    Identified the death modality engaged by COPS8 loss, showing the CSN suppresses RIPK1-RIPK3-MLKL-dependent necroptosis, with pharmacological and genetic rescue extending lifespan.

    Evidence Conditional Cops8 KO mice with necroptosis-protein blots, Evans blue uptake, Nec-1 treatment, and RIPK3 haploinsufficiency

    PMID:32578441

    Open questions at the time
    • Molecular link between CSN dysfunction and RIPK1-RIPK3 activation not defined
    • Whether a CRL substrate gates necroptosis unknown
  12. 2020 Medium

    Implicated COPS8 in tumor cell EMT and dormancy via NF-κB-driven HIF-1α transcription and HIF-1α protein stabilization, expanding its signaling roles in cancer.

    Evidence Gain/loss-of-function in colorectal cancer cells, xenografts, NF-κB reporter, and HIF-1α ubiquitination assays

    PMID:33261601

    Open questions at the time
    • Mechanism of HIF-1α de-ubiquitination by CSN8 not biochemically resolved
    • Single-lab study
  13. 2022 Medium

    Placed COPS8 downstream of AhR signaling in intestinal epithelium as a driver of anti-microbial peptide induction and colitis protection, defining a mucosal-defense role.

    Evidence Gut epithelium-specific Cops8 knockout mice, DSS colitis model, and AhR pathway epistasis

    PMID:34994476

    Open questions at the time
    • Molecular mechanism connecting COPS8 to anti-microbial peptide expression not defined
    • Single study

Open questions

Synthesis pass · forward-looking unresolved questions
  • The specific cullin-RING ligase substrates whose dysregulation drives the survival, proliferation, necroptosis, and mucosal-defense phenotypes of COPS8 loss remain unidentified, and the biochemical basis for its reported non-CSN roles in NF-κB/HIF-1α signaling is undefined.
  • No critical CRL substrate mapped to a specific phenotype
  • Mechanism of NF-κB and HIF-1α regulation not biochemically resolved
  • Direct vs. indirect contribution to necroptosis activation unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 2 GO:0005654 nucleoplasm 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-1640170 Cell Cycle 3 R-HSA-162582 Signal Transduction 2 R-HSA-168256 Immune System 2 R-HSA-9612973 Autophagy 2 R-HSA-5357801 Programmed Cell Death 1
Partners
CSN2CSN3CSN4CSN5CSN6CSN7
Complex memberships
COP9 signalosome (CSN)

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 Cardiomyocyte-restricted knockout of Csn8 in mice impaired CSN holocomplex formation and cullin deneddylation, caused decreases in F-box proteins, severe UPS dysfunction (demonstrated with surrogate misfolded protein), massive cardiomyocyte necrosis, cardiac hypertrophy, and heart failure, establishing that COPS8/CSN8 is essential for cullin deneddylation, UPS-mediated protein degradation, and cardiomyocyte survival in the postnatal heart. Conditional cardiomyocyte-restricted Cre-LoxP Csn8 knockout in mice; cullin neddylation western blot; UPS surrogate substrate assay; histology; electron microscopy Circulation research High 21051661
2011 Cardiomyocyte-restricted Csn8 knockout caused marked accumulation of autophagosomes and defective autophagosome maturation (impaired autophagosome removal), accompanied by downregulation of Rab7. Restoring Rab7 or inhibiting its knockdown rescued autophagosome maturation, establishing that COPS8/CSN regulates autophagosome maturation likely through controlling Rab7 expression. Conditional Csn8 KO in mouse hearts; GFP-LC3 imaging; electron microscopy of autophagic vacuole stages; autophagic flux assessment; Rab7 immunofluorescence co-localization; Rab7 siRNA knockdown in cultured cardiomyocytes Circulation High 21986281
2013 Conditional ablation of Csn8 in adult mouse cardiomyocytes caused accumulation of neddylated cullins (and non-cullin proteins), increased ubiquitinated proteins, stabilization of a proteasome surrogate substrate, impaired autophagic flux with autophagosome accumulation, increased oxidized proteins, massive cardiomyocyte necrosis, and dilated cardiomyopathy, demonstrating that CSN8/CSN is indispensable to both proteasome-mediated proteolysis and the autophagic-lysosomal pathway in adult hearts. Temporally controlled Cre-LoxP conditional Csn8 ablation in adult mice; western blotting for neddylated cullins; UPS surrogate substrate assay; autophagic flux assessment; histology; echocardiography Circulation. Heart failure High 23873473
2015 CSN8 hypomorphism in mice markedly increased neddylated cullins in the myocardium and significantly reduced capacity to degrade a surrogate misfolded protein. Introduction of CSN8 hypomorphism into CryABR120G proteinopathic mice aggravated cardiomyopathy and protein aggregate accumulation. In cultured cardiomyocytes, CSN8 knockdown suppressed ubiquitination and degradation of misfolded CryABR120G but not native CryAB, establishing that COPS8/CSN promotes cullin-RING ligase-dependent degradation of cytosolic misfolded proteins and protects against cardiac proteotoxicity. CSN8 hypomorphic mice crossed with CryABR120G proteinopathy mice; UPS surrogate substrate assay; CSN8 siRNA knockdown in cardiomyocytes; ubiquitination assays; protein aggregate quantification; cullin-RING ligase inhibition Circulation research High 26383969
2007 Conditional deletion of Csn8 in peripheral T lymphocytes disrupted CSN holocomplex formation, reduced T cell survival and proliferation in vivo, impaired antigen-induced IL-2 production, and caused defective G0-to-cell cycle entry. This was associated with failure to induce G1 cyclins and CDKs and with excessive p21Cip1 induction, defining a CSN8-dependent transcriptional control pathway required for antigen-induced T cell proliferation. Conditional T cell-specific Csn8 knockout mice; flow cytometry for cell cycle; BrdU incorporation; cytokine ELISA; qRT-PCR for cell cycle gene expression; western blotting for p21 Nature immunology High 17906629
2010 Postnatal hepatocyte-restricted knockout of Csn8 in mice differentially downregulated all other CSN subunits and significantly impaired deneddylation of all cullins examined, caused massive hepatocyte apoptosis, diminished hepatocyte proliferative response to injury, and produced hepatocytomegaly with dysplastic nuclear features, establishing that COPS8/CSN8 is required for postnatal hepatocyte survival and effective proliferation. Hepatocyte-restricted Cre-LoxP Csn8 KO; western blotting for CSN subunits and neddylated cullins; TUNEL apoptosis assay; BrdU proliferation; histopathology Cell death and differentiation High 20689553
2020 Cardiomyocyte-restricted Csn8 knockout (Cops8-cko) mice exhibited elevated RIPK1, RIPK3, MLKL, RIPK1-bound RIPK3, and suppressed caspase-8 activity. RIPK1 kinase inhibitor Nec-1 reduced Evans blue dye-positive (necrotic) cardiomyocytes and extended median lifespan in Cops8-cko mice; RIPK3 haploinsufficiency had similar rescuing effects. This established that COPS8/COP9 signalosome suppresses RIPK1-RIPK3-dependent cardiomyocyte necroptosis. Conditional Cops8 KO mice; western blotting for necroptosis pathway proteins; Evans blue dye uptake assay; pharmacological RIPK1 inhibition (Nec-1); genetic RIPK3 haploinsufficiency; caspase-8 activity assay; Cyclophilin D KO as negative control Circulation. Heart failure High 32578441
2001 A cytoplasmic CSN subcomplex (~100 kDa) containing CSN4-8 (but not CSN1-3) was identified by glycerol gradient and cell fractionation, with this smaller complex mainly located in the cytoplasm and sensitive to leptomycin B. Ectopic expression of CSN8, along with CSN3, CSN6, and CSN7, was capable of inducing p27 downregulation. The data indicate CSN8 is a component of a cytoplasmic CRM1-dependent export subcomplex that participates in p27 degradation. Glycerol gradient sedimentation; cellular fractionation; leptomycin B treatment; ectopic expression of individual CSN subunits; p27 protein level assay The Journal of biological chemistry Medium 11704659
2008 Down-regulation of CSN8 by RNAi in HEK293 cells destabilized other CSN subunits, reduced CSN holocomplex levels, increased neddylated cullin proteins, reduced F-box protein Skp2, enhanced degradation of a proteasome surrogate substrate and cyclin kinase inhibitor p21, and reduced p21 and p27 transcript levels, demonstrating that CSN8 is required to maintain CSN complex integrity, cullin deneddylation, and proteasome regulation of key cell cycle inhibitors. siRNA knockdown of CSN8 in HEK293 cells; western blotting for CSN subunits, neddylated cullins, Skp2, p21, p27; proteasome surrogate substrate assay; RT-PCR for p21/p27 transcripts The international journal of biochemistry & cell biology Medium 18706515
2012 miR-146a was identified as directly targeting COPS8 mRNA in gastric cancer cells (confirmed by qPCR, western blotting, and luciferase assays). COPS8 was shown to be part of the G protein-coupled receptor (GPCR) pathway of NF-κB activation. Overexpression of miR-146a inhibited LPA-induced NF-κB activation and reduced LPA-induced tumor-promoting cytokines, placing COPS8 as a component of GPCR-NF-κB signaling downstream of LPA. miR-146a transfection; qPCR; western blotting; luciferase 3'UTR reporter assay; NF-κB activity assay; cytokine measurement after LPA stimulation Molecular cancer Medium 22992343
2022 Using gut epithelium-specific COPS8 knockout mice, COPS8 was shown to act downstream of the AhR signaling pathway and is required for the induction of anti-microbial peptides in intestinal epithelial cells. Mulberry bark exosome-like nanoparticles activate AhR, leading to COPS8 induction, which in turn drives anti-microbial peptide expression and protection against colitis. Gut epithelium-specific Cops8 conditional knockout mice; DSS colitis model; AhR pathway assays; anti-microbial peptide measurement; epistasis analysis placing COPS8 downstream of AhR EMBO reports Medium 34994476
2014 Dynamic regulation of COP9 signalosome upon UV DNA damage included upregulation of specific phosphorylations within CSN8 (along with CSN1 and CSN3), as detected by mass spectrometry-based phosphoproteomics. UV damage caused dose-dependent temporal shuttling of the CSN complex into the nucleus. The CSN complex was found in cytoplasm, nucleoplasm, and chromatin-bound fractions with different posttranslational modification profiles. Biochemical fractionation; fluorescence microscopy; mass spectrometry-based phosphoproteomics; UV damage time-course experiments Molecular and cellular biology Medium 24421388
2012 A CSN4-5-6-7 subcomplex was reconstituted biochemically, with CSN8 shown to interact with the CSN4-6-7 core. Pairwise and combinatorial interactions were characterized: MPN-MPN between CSN5 and CSN6, PCI-PCI between CSN4 and CSN7, and interactions mediated through the CSN6 C-terminus with CSN4 and CSN7. CSN8 was found to interact with the CSN4-6-7 heterotrimer, establishing its position in subcomplex assembly. Bacterial co-expression reconstitution; in vitro pull-down; size-exclusion chromatography; analytical ultracentrifugation The Journal of biological chemistry Medium 23086934
2009 Overexpression of CSN2 in HEK293 cells increased endogenous CSN7 and CSN8 protein levels and decreased ubiquitinated forms of ABCA1, demonstrating that assembled CSN (containing CSN8) controls the ubiquitinylation status of ABCA1. Co-immunoprecipitation; western blotting; overexpression of CSN2 in HEK293 cells; MG132 proteasome inhibition Biochemical and biophysical research communications Low 19268428
2020 CSN8 expression increased significantly in colorectal cancer tissues. CSN8 overexpression in colorectal cancer cells induced EMT, arrested cell proliferation, upregulated dormancy markers (NR2F1, DEC2, p27) and hypoxia response genes (HIF-1α, GLUT1). CSN8 silencing blocked hypoxia-induced EMT and dormancy. CSN8 regulated EMT and dormancy partly by activating NF-κB to increase HIF-1α mRNA and by stabilizing HIF-1α protein via HIF-1α de-ubiquitination. CSN8 overexpression and siRNA knockdown in colorectal cancer cells; in vivo xenograft; EMT marker western blotting; NF-κB reporter assay; HIF-1α ubiquitination assay; dormancy marker measurement; hypoxia experiments Molecular cancer Medium 33261601

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 The COP9 signalosome. Annual review of cell and developmental biology 391 14570571
2003 COP9 signalosome: a multifunctional regulator of SCF and other cullin-based ubiquitin ligases. Cell 347 14505567
2008 The COP9 signalosome: more than a protease. Trends in biochemical sciences 336 18926707
2001 COP9 signalosome-specific phosphorylation targets p53 to degradation by the ubiquitin system. The EMBO journal 314 11285227
2002 Role of SCF ubiquitin-ligase and the COP9 signalosome in the N gene-mediated resistance response to Tobacco mosaic virus. The Plant cell 253 12119369
2001 The cytoplasmic shuttling and subsequent degradation of p27Kip1 mediated by Jab1/CSN5 and the COP9 signalosome complex. The Journal of biological chemistry 252 11704659
1998 The COP9 complex is conserved between plants and mammals and is related to the 26S proteasome regulatory complex. Current biology : CB 210 9707402
2016 Cullin-RING ubiquitin E3 ligase regulation by the COP9 signalosome. Nature 182 27029275
2001 COP9 signalosome revisited: a novel mediator of protein degradation. Trends in cell biology 172 11567875
2003 Cop9/signalosome subunits and Pcu4 regulate ribonucleotide reductase by both checkpoint-dependent and -independent mechanisms. Genes & development 162 12695334
2003 The COP9 signalosome: an assembly and maintenance platform for cullin ubiquitin ligases? Nature cell biology 162 14647295
2003 Protein kinase CK2 and protein kinase D are associated with the COP9 signalosome. The EMBO journal 161 12628923
2003 The COP9 signalosome interacts physically with SCF COI1 and modulates jasmonate responses. The Plant cell 161 12724535
2001 JAB1/CSN5 and the COP9 signalosome. A complex situation. EMBO reports 152 11258719
2022 Exosome-like nanoparticles from Mulberry bark prevent DSS-induced colitis via the AhR/COPS8 pathway. EMBO reports 148 34994476
2016 Targeted inhibition of the COP9 signalosome for treatment of cancer. Nature communications 147 27774986
2002 The COP9 signalosome: at the interface between signal transduction and ubiquitin-dependent proteolysis. Journal of cell science 137 11861754
1999 COP9 signalosome-directed c-Jun activation/stabilization is independent of JNK. The Journal of biological chemistry 124 10585392
1999 The COP9/signalosome complex is conserved in fission yeast and has a role in S phase. Current biology : CB 124 10607571
2009 Mammalian COP9 signalosome. Genes to cells : devoted to molecular & cellular mechanisms 122 19849719
2003 Disruption of the COP9 signalosome Csn2 subunit in mice causes deficient cell proliferation, accumulation of p53 and cyclin E, and early embryonic death. Molecular and cellular biology 117 12972599
2011 Roles of COP9 signalosome in cancer. Cell cycle (Georgetown, Tex.) 116 21876386
2004 The COP9 signalosome (CSN): an evolutionary conserved proteolysis regulator in eukaryotic development. Biochimica et biophysica acta 111 15571808
2003 The COP9 signalosome: regulating plant development through the control of proteolysis. Annual review of plant biology 111 14502989
2003 The COP9 signalosome promotes degradation of Cyclin E during early Drosophila oogenesis. Developmental cell 101 12737805
2011 COP9 signalosome regulates autophagosome maturation. Circulation 98 21986281
2002 Deletion mutants in COP9/signalosome subunits in fission yeast Schizosaccharomyces pombe display distinct phenotypes. Molecular biology of the cell 98 11854407
2007 COP9 signalosome subunit 8 is essential for peripheral T cell homeostasis and antigen receptor-induced entry into the cell cycle from quiescence. Nature immunology 97 17906629
2005 The emerging role of the COP9 signalosome in cancer. Molecular cancer research : MCR 97 16380502
2009 The COP9 signalosome mediates beta-catenin degradation by deneddylation and blocks adenomatous polyposis coli destruction via USP15. Journal of molecular biology 94 19576224
2010 Perturbation of cullin deneddylation via conditional Csn8 ablation impairs the ubiquitin-proteasome system and causes cardiomyocyte necrosis and dilated cardiomyopathy in mice. Circulation research 93 21051661
2020 COP9 signalosome: Discovery, conservation, activity, and function. Journal of integrative plant biology 90 31894894
2009 Revisiting the COP9 signalosome as a transcriptional regulator. EMBO reports 88 19305390
2012 microRNA-146a inhibits G protein-coupled receptor-mediated activation of NF-κB by targeting CARD10 and COPS8 in gastric cancer. Molecular cancer 86 22992343
2000 Electron microscopy and subunit-subunit interaction studies reveal a first architecture of COP9 signalosome. Journal of molecular biology 86 10903862
2016 Structural and kinetic analysis of the COP9-Signalosome activation and the cullin-RING ubiquitin ligase deneddylation cycle. eLife 84 27031283
2008 Targeted inactivation of the COP9 signalosome impairs multiple stages of T cell development. The Journal of experimental medicine 70 18268034
2018 The COP9 Signalosome regulates seed germination by facilitating protein degradation of RGL2 and ABI5. PLoS genetics 69 29462139
1999 Comparison of human COP9 signalsome and 26S proteasome lid'. Molecular biology reports 69 10363643
2010 The COP9 signalosome mediates transcriptional and metabolic response to hormones, oxidative stress protection and cell wall rearrangement during fungal development. Molecular microbiology 68 21062371
2010 Structural insights into the COP9 signalosome and its common architecture with the 26S proteasome lid and eIF3. Structure (London, England : 1993) 64 20399188
2005 Consequences of COP9 signalosome and 26S proteasome interaction. The FEBS journal 64 16045761
2010 Fungal development and the COP9 signalosome. Current opinion in microbiology 63 20934903
2006 The COP9 signalosome regulates Skp2 levels and proliferation of human cells. The Journal of biological chemistry 63 16943200
2004 The Jab1/COP9 signalosome subcomplex is a downstream mediator of Bcr-Abl kinase activity and facilitates cell-cycle progression. Blood 63 15353483
2002 Conservation of the COP9/signalosome in budding yeast. BMC genetics 63 12186635
2020 The COP9 Signalosome: A Multi-DUB Complex. Biomolecules 61 32708147
2009 COP9-associated CSN5 regulates exosomal protein deubiquitination and sorting. The American journal of pathology 59 19246649
1996 det1, cop1, and cop9 mutations cause inappropriate expression of several gene sets. The Plant cell 58 8953766
2020 CSN8 is a key regulator in hypoxia-induced epithelial-mesenchymal transition and dormancy of colorectal cancer cells. Molecular cancer 56 33261601
2014 Protein competition switches the function of COP9 from self-renewal to differentiation. Nature 54 25119050
2013 The COP9 signalosome is required for autophagy, proteasome-mediated proteolysis, and cardiomyocyte survival in adult mice. Circulation. Heart failure 54 23873473
2009 The COP9 signalosome and its role in plant development. European journal of cell biology 54 20036030
2011 The COP9 signalosome controls jasmonic acid synthesis and plant responses to herbivory and pathogens. The Plant journal : for cell and molecular biology 53 21265900
2011 COP9 signalosome subunit 6 stabilizes COP1, which functions as an E3 ubiquitin ligase for 14-3-3σ. Oncogene 53 21625211
2003 The COP9 signalosome: an alternative lid for the 26S proteasome? Trends in cell biology 53 14507477
2015 Diversity of COP9 signalosome structures and functional consequences. FEBS letters 52 26096786
2022 The COP9 signalosome: A versatile regulatory hub of Cullin-RING ligases. Trends in biochemical sciences 49 36041947
2007 Downregulation of COP9 signalosome subunits differentially affects the CSN complex and target protein stability. BMC biochemistry 49 18093314
2017 Inhibition of atherogenesis by the COP9 signalosome subunit 5 in vivo. Proceedings of the National Academy of Sciences of the United States of America 48 28292897
2003 The COP9 signalosome-like complex in S. cerevisiae and links to other PCI complexes. The international journal of biochemistry & cell biology 48 12672462
2015 CSNAP Is a Stoichiometric Subunit of the COP9 Signalosome. Cell reports 47 26456823
2004 The COP9 signalosome: mediating between kinase signaling and protein degradation. Current protein & peptide science 43 15180523
2016 Inositol hexakisphosphate (IP6) generated by IP5K mediates cullin-COP9 signalosome interactions and CRL function. Proceedings of the National Academy of Sciences of the United States of America 40 26976604
2014 Plant COP9 signalosome subunit 5, CSN5. Plant science : an international journal of experimental plant biology 40 24908506
2015 Inhibition of COP9-signalosome (CSN) deneddylating activity and tumor growth of diffuse large B-cell lymphomas by doxycycline. Oncotarget 38 26142707
2011 COP9 signalosome function in the DDR. FEBS letters 37 21510940
2015 COP9 signalosome controls the degradation of cytosolic misfolded proteins and protects against cardiac proteotoxicity. Circulation research 36 26383969
2007 Retinoblastoma protein regulation by the COP9 signalosome. Molecular biology of the cell 36 17251548
2015 The Role of the COP9 Signalosome and Neddylation in DNA Damage Signaling and Repair. Biomolecules 35 26437438
2000 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. The Journal of biological chemistry 34 10991940
2016 Constitutive photomorphogenesis protein 1 (COP1) and COP9 signalosome, evolutionarily conserved photomorphogenic proteins as possible targets of melatonin. Journal of pineal research 33 27121162
2012 HER2-Akt signaling in regulating COP9 signalsome subunit 6 and p53. Cell cycle (Georgetown, Tex.) 33 23095642
2007 The ubiquitin- and proteasome-dependent degradation of COX-2 is regulated by the COP9 signalosome and differentially influenced by coxibs. Journal of molecular medicine (Berlin, Germany) 33 17429597
2015 The COP9 signalosome is vital for timely repair of DNA double-strand breaks. Nucleic acids research 32 25855810
2020 Basis for metabolite-dependent Cullin-RING ligase deneddylation by the COP9 signalosome. Proceedings of the National Academy of Sciences of the United States of America 31 32047038
2013 PDLIM2 regulates transcription factor activity in epithelial-to-mesenchymal transition via the COP9 signalosome. Molecular biology of the cell 31 24196835
2011 Many jobs for one good cop - the COP9 signalosome guards development and defense. Plant science : an international journal of experimental plant biology 31 22325866
2009 The COP9 signalosome controls ubiquitinylation of ABCA1. Biochemical and biophysical research communications 31 19268428
2013 Crystal structure and versatile functional roles of the COP9 signalosome subunit 1. Proceedings of the National Academy of Sciences of the United States of America 30 23818606
2012 CDK inhibitor p57 (Kip2) is negatively regulated by COP9 signalosome subunit 6. Cell cycle (Georgetown, Tex.) 30 23187808
2006 The COP9 signalosome regulates cell proliferation of Dictyostelium discoideum. European journal of cell biology 30 16781008
2009 COP9 signalosome controls the Carma1-Bcl10-Malt1 complex upon T-cell stimulation. EMBO reports 29 19444310
2008 The COP9 signalosome negatively regulates proteasome proteolytic function and is essential to transcription. The international journal of biochemistry & cell biology 28 18706515
2015 COP9-Hedgehog axis regulates the function of the germline stem cell progeny differentiation niche in the Drosophila ovary. Development (Cambridge, England) 27 26672093
2014 Structural and biochemical characterization of the Cop9 signalosome CSN5/CSN6 heterodimer. PloS one 27 25144743
2012 The organization of a CSN5-containing subcomplex of the COP9 signalosome. The Journal of biological chemistry 27 23086934
2010 Control of NF-kappaB activation by the COP9 signalosome. Biochemical Society transactions 27 20074051
2019 Role of Cop9 Signalosome Subunits in the Environmental and Hormonal Balance of Plant. Biomolecules 26 31181827
2007 The subunit CSN6 of the COP9 signalosome is cleaved during apoptosis. The Journal of biological chemistry 26 17337451
2003 On again-off again: COP9 signalosome turns the key on protein degradation. Current opinion in plant biology 26 14611949
2018 Renal COP9 Signalosome Deficiency Alters CUL3-KLHL3-WNK Signaling Pathway. Journal of the American Society of Nephrology : JASN 25 30301860
2021 Desmosomal COP9 regulates proteome degradation in arrhythmogenic right ventricular dysplasia/cardiomyopathy. The Journal of clinical investigation 23 33857019
2020 COP9 signalosome is an essential and druggable parasite target that regulates protein degradation. PLoS pathogens 23 32960936
2019 Role of the COP9 Signalosome (CSN) in Cardiovascular Diseases. Biomolecules 23 31195722
2020 COP9 Signalosome Suppresses RIPK1-RIPK3-Mediated Cardiomyocyte Necroptosis in Mice. Circulation. Heart failure 22 32578441
2014 Dynamic regulation of the COP9 signalosome in response to DNA damage. Molecular and cellular biology 22 24421388
2020 Thrombin-Par1 signaling axis disrupts COP9 signalosome subunit 3-mediated ABCA1 stabilization in inducing foam cell formation and atherogenesis. Cell death and differentiation 21 32968199
2019 COP9 Signalosome Interaction with UspA/Usp15 Deubiquitinase Controls VeA-Mediated Fungal Multicellular Development. Biomolecules 21 31216760
2010 COP9 signalosome subunit 8 is required for postnatal hepatocyte survival and effective proliferation. Cell death and differentiation 20 20689553

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