IndraLab
Statements
reach
"These data suggests a hierarchy in the catalytic activity over the enzymatic system and the substrate type, with the inactive CSN5 DeltaC, WT form, CSN5 DeltaC, R106T that has basal activity, the MPN heterodimer alone that has robust isopeptidase activity on non physiological substrates and the CSN5 and CSN6 heterodimer in the context of CSN that recapitulates strong activity on both non physiological and physiological substrates."
COPS6 is modified
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COPS6 is phosphorylated.
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"These data imply that CSN6 possibly regulates the gene expression of SGOC genes and impacts SGOC amino acid metabolism through its negative impact on FOXO4 that transcriptionally suppresses the gene expression of SGOC genes.2.6
PKB/Akt-Mediated CSN6 Phosphorylation Enhances COP1-Regulated FOXO4 Ubiquitination and Subsequent Elevation of SGOC Genes."
sparser
"First, we have shown that S60 of CSN6 can be phosphorylated by PKB/Akt [ xref ] and that PKB/Akt enhances the steady‐state expression of CSN6. [ xref ] This S60 site is located in CSN6's MPN ( M pr1p and P ad1p N ‐terminal) domain, a domain found in the N‐terminus of yeast Mpr1 and Pad1 proteins. [ xref , xref , xref ] MPN domain contains polar residues that resemble the active site residues of metalloproteases [ xref ] and is involved in a proteasome‐associated deneddylation activity. [ xref ] Also the MPN domain is involved in heterodimerization between CSN6 and CSN5 to regulate Cullin neddylation. [ xref ] How S60 phosphorylation participates in any activity of the MPN domain remains to be identified."
COPS6 is ubiquitinated.
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2
sparser
"As CSN6‐FOXO4 axis impacts on the expression of Glut1, biochemical assays that quantitates the glucose uptake (consumption) by assessing uptake of (2‐( N ‐(7‐nitrobenz‐2‐oxa‐1,3‐diazol‐4‐yl)amino)‐2‐deoxyglucose (2‐NBDG)), a green fluorescent glucose analog, additionally demonstrated that CSN6 knockdown inhibited 2‐NBDG uptake (Figure xref ), while FOXO4 knockdown increased 2‐NBDG uptake (Figure xref )."
reach
"These data imply that CSN6 possibly regulates the gene expression of SGOC genes and impacts SGOC amino acid metabolism through its negative impact on FOXO4 that transcriptionally suppresses the gene expression of SGOC genes.2.6
PKB/Akt-Mediated CSN6 Phosphorylation Enhances COP1-Regulated FOXO4 Ubiquitination and Subsequent Elevation of SGOC Genes."
COPS6 affects cell population proliferation
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COPS6 activates cell population proliferation.
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COPS6 activates cell population proliferation. 10 / 20
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reach
"Through combinatorial effects on the MDM2-p53 signaling axis and now SKP2 mediated p57 Kip2 degradation, it is hypothesized that CSN6 overexpression can effectively promote cell proliferation by simultaneously relieving cell cycle restraints, apoptosis, senescence, and presumably p53 functions in DNA damage repair and cell metabolism, among other important tumor suppressive mechanisms."
COPS6 inhibits cell population proliferation.
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2
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"Noticeably, reduced expression of Csn6 in Emicro-Myc background can also contribute to p53 stabilization in 33% of Emicro-Myc and Csn6 +/- lymphomas when compared with Emicro-Myc and Csn6 +/+, suggesting that both CSN6 mediated p53 downregulation and CSN6 mediated Myc elevation contribute to lymphomagenesis of this system (XREF_FIG)."
reach
"Compared with empty vector transfected control cells, cells transfected with CSN6 had a decelerated endogenous Myc turnover rate (XREF_FIG); the pulse chase analyses of over expressed Myc with CSN6 or with shRNA mediated CSN6 knockdown indicated that over expression of CSN6 stabilized Myc while shRNA-CSN6 increased Myc degradation (XREF_FIG)."
sparser
"In addition, TRIM21’s function is associated with autoimmune diseases, such as systemic lupus erythematosus (SLE) and Sjögren’s syndrome. xref , xref Notably, patients with SLE or Sjögren’s syndrome have an increased risk for developing certain cancers, including non-Hodgkin’s lymphoma. xref In addition, TRIM21 interacts with endoglin, xref which is a prognostic marker in CRC xref and also act as a CSC marker in renal cell carcinoma. xref Future studies will need to address how the CSN6–TRIM21 axis may impact these signalling pathways to promote tumorigenesis."
reach
"We also found that CSN6 overexpression in melanoma cells could prolong the half-life of CDK9 and that the decrease in CDK9 protein expression in CSN6-knockdown cells could be obviously rescued in the presence of MG132, indicating that CSN6 regulates CDK9 stability by reducing CDK9 ubiquitination."
reach
"In addition, to investigate whether CSN6 controls the ubiquitination and degradation of the E3 ligase UBR5 to stabilize CDK9, in vivo ubiquitination assays were performed and found that CSN6 increased UBR5 ubiquitination levels and decreased CDK9 ubiquitination levels in melanoma cells and 293FT cells."
reach
"In addition, to investigate whether CSN6 controls the ubiquitination and degradation of the E3 ligase UBR5 to stabilize CDK9, in vivo ubiquitination assays were performed and found that CSN6 increased UBR5 ubiquitination levels and decreased CDK9 ubiquitination levels in melanoma cells and 293FT cells."
reach
"Immunoblotting analysis showed that EGF treatment decreased the steady‐state expression of FOXO4 within 45 min (Figure
1A, Figure S1A, Supporting Information) and accelerated turnover rate of FOXO4 (Figure S1B, Supporting Information) in several CRC cell lines, whereas the EGF induced the expression of CSN6 and COP1, an E3 ligase, within that period of time (Figure 1A, Figure S1A, Supporting Information)."
COPS6 affects Neoplasm Invasiveness
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COPS6 activates Neoplasm Invasiveness. 10 / 15
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eidos
"CSN6 promotes GBM proliferation , migration , invasion , and tumorigenesis through upregulation of EGFR by blocking its ubiquitination ; this happens as a result of interactions with CHIP that cause its degradation , although CHIP auto-ubiquitination occurs through an unknown mechanism [ 91 ] ."
reach
"Also, WT CSN6 increased cell migration and invasion in a wound healing assay (p < 0.001, XREF_FIG) and in transwell migration and invasion assays (XREF_FIG), whereas CSN6 S148A lost such capability, demonstrating that the CSN6 promoted migration and invasion of colon cancer cells requires a phosphorylation event."
COPS6 activates Neoplasm Invasiveness. 1 / 1
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COPS6 affects Snail1
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sparser
"In addition, TRIM21’s function is associated with autoimmune diseases, such as systemic lupus erythematosus (SLE) and Sjögren’s syndrome. xref , xref Notably, patients with SLE or Sjögren’s syndrome have an increased risk for developing certain cancers, including non-Hodgkin’s lymphoma. xref In addition, TRIM21 interacts with endoglin, xref which is a prognostic marker in CRC xref and also act as a CSC marker in renal cell carcinoma. xref Future studies will need to address how the CSN6–TRIM21 axis may impact these signalling pathways to promote tumorigenesis."
sparser
"As CSN6‐FOXO4 axis impacts on the expression of Glut1, biochemical assays that quantitates the glucose uptake (consumption) by assessing uptake of (2‐( N ‐(7‐nitrobenz‐2‐oxa‐1,3‐diazol‐4‐yl)amino)‐2‐deoxyglucose (2‐NBDG)), a green fluorescent glucose analog, additionally demonstrated that CSN6 knockdown inhibited 2‐NBDG uptake (Figure xref ), while FOXO4 knockdown increased 2‐NBDG uptake (Figure xref )."
COPS6 affects Neoplasm Metastasis
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COPS6 activates Neoplasm Metastasis. 10 / 12
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eidos
"CSN6 promotes melanoma proliferation and metastasis by controlling the UBR5-mediated ubiquitination and degradation of CDK9 As a critical subunit of the constitutive photomorphogenesis 9 ( COP9 ) signalosome ( CSN ) , CSN6 is upregulated in some human cancers and plays critical roles in tumorigenesis and progression , but its biological functions and molecular mechanisms in melanoma remain unknown ."
reach
"In addition, to investigate whether CSN6 controls the ubiquitination and degradation of the E3 ligase UBR5 to stabilize CDK9, in vivo ubiquitination assays were performed and found that CSN6 increased UBR5 ubiquitination levels and decreased CDK9 ubiquitination levels in melanoma cells and 293FT cells."
sparser
"In addition to demonstrating amplification of the CSN6 gene locus at 7q22.1 in human mammary tumors, xref they report that AKT phosphorylation at Ser60 stabilizes CSN6. xref Interestingly, by promoting 14–3-3σ degradation through stabilization of its E3-ligase COP1, CSN6 can activate AKT to create a self-propelling positive feedback loop xref ( xref )."
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"Through combinatorial effects on the MDM2-p53 signaling axis and now SKP2 mediated p57 Kip2 degradation, it is hypothesized that CSN6 overexpression can effectively promote cell proliferation by simultaneously relieving cell cycle restraints, apoptosis, senescence, and presumably p53 functions in DNA damage repair and cell metabolism, among other important tumor suppressive mechanisms."
reach
"Noticeably, reduced expression of Csn6 in Emicro-Myc background can also contribute to p53 stabilization in 33% of Emicro-Myc and Csn6 +/- lymphomas when compared with Emicro-Myc and Csn6 +/+, suggesting that both CSN6 mediated p53 downregulation and CSN6 mediated Myc elevation contribute to lymphomagenesis of this system (XREF_FIG)."
sparser
"The CSN6-COP1 axis has following physiological significance possibly: (1) CSN6 stabilizing COP1 directly enhances COP1-mediated p53 ubiquitination and degradation. (2) CSN6-COP1 axis causes 14-3-3σ degradation, which on the one hand, can block 14-3-3σ’s positive effect on p53 stability, on the other hand, activates Akt and promotes Akt-mediated cell survival."
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COPS6 activates epithelial to mesenchymal transition.
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COPS6 increases the amount of epithelial to mesenchymal transition.
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COPS6 affects cell migration
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COPS6 activates cell migration. 7 / 7
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"Also, WT CSN6 increased cell migration and invasion in a wound healing assay (p < 0.001, XREF_FIG) and in transwell migration and invasion assays (XREF_FIG), whereas CSN6 S148A lost such capability, demonstrating that the CSN6 promoted migration and invasion of colon cancer cells requires a phosphorylation event."
COPS6 affects E3_Ub_ligase
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COPS6 binds E3_Ub_ligase.
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COPS6 activates E3_Ub_ligase.
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COPS6 affects cell growth
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COPS6 affects Aldh1a1 mRNA
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Pirinixic acid affects COPS6
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eidos
"Cells with high ALDH1A1 levels have increased expression levels of vimentin , matrix metalloproteinase-2 ( MMP2 ) , MMP7 and MMP9 , which are implicated in epithelial-mesenchymal transition and metastatic capabilities.40 Interestingly , CSN6 is able to promote the expression of ALDH1A1 , a known CSC marker upregulated in cancer spheroids.41 Chromatin immunoprecipitation assays have characterised ALDH1A1 as a direct target of beta-catenin activation ."
reach
"In another study, quercetin inhibited the viability of HT29 cells, caused cell shrinkage, chromatin condensation, and nuclear collapse, lessened the protein expression levels of phosphorylated-Akt, and augmented the protein degradation of constitutive photomorphogenesis 6 signalosome (CSN6) (Yang et al., 2016)."
Snail1 affects COPS6
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MPN domain affects COPS6
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sparser
"These results show that the CSN complex bear only one copy of Csn6, either a full-length or a truncated form (S6CD); while the MPN − domain fragment of Csn6, when expressed without the S6CD and incapable of integrating into the CSN complex, can still interact with over-stoichiometric amounts of Flag-Csn6 ( xref , xref , xref )."
E3_Ub_ligase affects COPS6
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CSN3 affects COPS6
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COPS6 affects nucleotide metabolic process
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COPS6 affects migration
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eidos
"CSN6 promotes GBM proliferation , migration , invasion , and tumorigenesis through upregulation of EGFR by blocking its ubiquitination ; this happens as a result of interactions with CHIP that cause its degradation , although CHIP auto-ubiquitination occurs through an unknown mechanism [ 91 ] ."
COPS6 affects apoptotic process
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COPS6 inhibits apoptotic process. 3 / 3
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reach
"Through combinatorial effects on the MDM2-p53 signaling axis and now SKP2 mediated p57 Kip2 degradation, it is hypothesized that CSN6 overexpression can effectively promote cell proliferation by simultaneously relieving cell cycle restraints, apoptosis, senescence, and presumably p53 functions in DNA damage repair and cell metabolism, among other important tumor suppressive mechanisms."
COPS6 affects Snail1 protein
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COPS6 affects MPN domain
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sparser
"These results show that the CSN complex bear only one copy of Csn6, either a full-length or a truncated form (S6CD); while the MPN − domain fragment of Csn6, when expressed without the S6CD and incapable of integrating into the CSN complex, can still interact with over-stoichiometric amounts of Flag-Csn6 ( xref , xref , xref )."
COPS6 affects CSN3
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COPS6 affects A0A288CFT1
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COPS5 affects MPN domain
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COPS5 affects CSN3
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A0A288CFT1 affects COPS6
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Cobalt dichloride affects COPS6
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Caspase recruitment domain affects COPS6
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Ser148 affects MAPK1
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MAPK1 affects Ser148
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MAPK1 affects Leu163
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Leu163 affects MAPK1
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HIV1gp4 affects COPS6
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Delta(9)-tetrahydrocannabinol affects COPS6
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Delta(9)-tetrahydrocannabinol increases the amount of COPS6.
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Delta(9)-tetrahydrocannabinol decreases the amount of COPS6.
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CUL affects CSN2
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CSNAP affects COPS6
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CSN2 affects CUL
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COPS6 affects v-myc avian myelocytomatosis viral oncogene homolog
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COPS6 affects turnover OCT1
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COPS6 affects steady-state TRIM21
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eidos
"Tripartite motif ( TRIM ) protein family members ( numbering > 70 ) have been implicated in various cellular functions , including cell proliferation , differentiation , development , apoptosis , antiviral activity , autophagy and oncogenesis.44 TRIM21 plays a pivotal role in immune activation during pathogen infection , but its cellular function remains unclear.45 Interestingly , CSN6 is able to decrease the steady-state expression of TRIM21 by enhancing TRIM21 ubiquitination , thereby promoting cancer stemness ."
COPS6 affects pathway
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COPS6 affects interleukin-6 production
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COPS6 affects cell migration breast cancer cells
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eidos
"CSN6 promotes the cell migration of breast cancer cells by positively regulating Snail1 stability Background : CSN6 , a subunit of the highly conserved constitutive photomorphogenesis 9 ( COP9 ) signalosome ( CSN ) , has been reported to be implicated in tumor progression in various kinds of malignant tumors ."
COPS6 affects cell cycle
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COPS6 inhibits cell cycle. 2 / 2
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reach
"Through combinatorial effects on the MDM2-p53 signaling axis and now SKP2 mediated p57 Kip2 degradation, it is hypothesized that CSN6 overexpression can effectively promote cell proliferation by simultaneously relieving cell cycle restraints, apoptosis, senescence, and presumably p53 functions in DNA damage repair and cell metabolism, among other important tumor suppressive mechanisms."
COPS6 affects caspase recruitment domain
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COPS6 affects activity
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COPS6 affects Snail1 stability
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COPS6 affects Ser148
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eidos
"CSN6 promotes melanoma proliferation and metastasis by controlling the UBR5-mediated ubiquitination and degradation of CDK9 As a critical subunit of the constitutive photomorphogenesis 9 ( COP9 ) signalosome ( CSN ) , CSN6 is upregulated in some human cancers and plays critical roles in tumorigenesis and progression , but its biological functions and molecular mechanisms in melanoma remain unknown ."
COPS6 affects HIV1gp4
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COPS6 affects Carcinogenesis
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COPS6 activates Carcinogenesis. 1 / 2
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eidos
"CSN6 promotes GBM proliferation , migration , invasion , and tumorigenesis through upregulation of EGFR by blocking its ubiquitination ; this happens as a result of interactions with CHIP that cause its degradation , although CHIP auto-ubiquitination occurs through an unknown mechanism [ 91 ] ."
COPS6 affects CSNAP
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COPS6 affects CRC PDOs
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COPS6 affects A375
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COPS6 affects 14-3-3sigma
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COPS6 affects 3',5'-cyclic AMP
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A375 affects COPS6
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17alpha-ethynylestradiol affects COPS6
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Valproic acid affects COPS6
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Tert-butyl hydroperoxide affects COPS6
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Methylmercury chloride affects COPS6
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Is overexpressed cancers affects COPS6
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Hsa-miR-328-3p affects COPS6
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Hsa-let-7i-5p affects COPS6
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Hsa-let-7c-5p affects COPS6
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Dichloroacetic acid affects COPS6
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Diarsenic trioxide affects COPS6
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Copper(II) sulfate affects COPS6
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Clofibrate affects COPS6
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Bisphenol A affects COPS6
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Benzo[a]pyrene affects COPS6
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UBR5 affects A375
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SKP2 affects E3_Ub_ligase
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reach
"29
The latest research showed that constitutive photomorphogenic 9 signalosome complex subunit 6 (CSN6) and plant homeodomain finger protein 19 (PHF19) exacerbate the pathological myocardial hypertrophy induced by Ang II by inhibiting the expression of SIRT2, and the overexpression of SIRT2 can reduce the effect of CSN6 in promoting myocardial hypertrophy."
RING-box protein 1 affects CUL
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MDM2-p53 affects COPS6
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IGHV3OR15-7 affects COPS6
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EPB41L4A-DT affects COPS6
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EGFR-ERK affects COPS6
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EGF-ERK2 Axis affects COPS6
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E3_Ub_ligase affects SKP2
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CUL affects RING-box protein 1
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CSN7 subfamily affects COPS6
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CSN2 affects csn
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CSN2 affects RING-box protein 1
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CSN2 affects RBX1
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COPS6 affects ubiquitination degradation cancer associated proteins
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COPS6 affects ubiquitination OCT1
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COPS6 affects ubiquitin proteasome
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COPS6 affects ubiquitin proteasome system-mediated Nkx2.2 protein
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COPS6 affects turnover TRIM21 protein
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COPS6 affects tumour-formation diluted
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COPS6 affects tumour growth
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COPS6 affects tumorigenicity
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COPS6 affects tumorigenicity Figure S17A-D
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COPS6 affects tumor growth
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COPS6 affects stemness marker aldehyde dehydrogenase A1
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COPS6 affects steady-state protein OCT1 ALDH1A1
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COPS6 affects steady-state FOXO4
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COPS6 affects spheres enriched
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COPS6 affects sphere-initiation
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COPS6 affects sphere-formation
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COPS6 affects sphere
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COPS6 affects soft agar colony
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COPS6 affects photomorphogenesis
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COPS6 inhibits photomorphogenesis. 1 / 1
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reach
"In another study, quercetin inhibited the viability of HT29 cells, caused cell shrinkage, chromatin condensation, and nuclear collapse, lessened the protein expression levels of phosphorylated-Akt, and augmented the protein degradation of constitutive photomorphogenesis 6 signalosome (CSN6) (Yang et al., 2016)."
COPS6 affects nucleotide
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COPS6 activates nucleotide. 1 / 1
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COPS6 affects migration breast cells
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COPS6 affects metastasis potential breast cancer cells
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COPS6 affects lipid biosynthetic process
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COPS6 activates lipid biosynthetic process. 1 / 1
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COPS6 affects lactate fructose-1
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COPS6 affects growth migration invasion melanoma cells
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COPS6 affects establishing CSN6-TRIM21-OCT1-ALDH1A1 stemness-promoting axis
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eidos
"OCT1 is known to regulate normal cell and CSC function.33 Loss of OCT1 in the colon was associated with restricted tumorigenicity.43 High OCT1 protein levels are correlated with the frequency of CD24 ( low ) / CD44 ( high ) cancer-initiating cells in primary malignant tissue.33 OCT1 is a transcription factor for ALDHs.27 Importantly , we show that CSN6 can reduce TRIM21-mediated OCT1 ubiquitination to regulate ALDH1A1 mRNA expression , thereby establishing the CSN6-TRIM21-OCT1-ALDH1A1 stemness-promoting axis ."
COPS6 affects decelerated turnover TRIM21
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COPS6 affects cycloheximide
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COPS6 inhibits cycloheximide. 1 / 1
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COPS6 affects cullin E3 ligases
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COPS6 affects criminal justice recidivism
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eidos
"HVIPs have been reported to reduce both trauma and criminal justice recidivism ( Cooper et al ., 2006 ; Shibru et al ., 2007 ) ; however , there is limited and mixed evidence to support their effectiveness ( Affinati et al ., 2016 ; Chong et al ., 2015 ; Cooper et al ., 2006 ; Dicker , 2016 ; Juillard et al ., 2016 ; Purtle et al ., 2013 ; Smith et al ., 2013 ) ."
COPS6 affects cellular senescence
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COPS6 inhibits cellular senescence. 1 / 1
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reach
"Through combinatorial effects on the MDM2-p53 signaling axis and now SKP2 mediated p57 Kip2 degradation, it is hypothesized that CSN6 overexpression can effectively promote cell proliferation by simultaneously relieving cell cycle restraints, apoptosis, senescence, and presumably p53 functions in DNA damage repair and cell metabolism, among other important tumor suppressive mechanisms."
COPS6 affects capacity BT549 MDA-MB-231 cell motility
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COPS6 affects cancer stemness
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COPS6 affects breast cancer cells
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COPS6 affects breast cancer cells migration is acknowledged
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COPS6 affects biosynthetic process
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COPS6 activates biosynthetic process. 1 / 1
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COPS6 affects ZO-1 gene
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COPS6 affects Ubiquitination
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COPS6 activates Ubiquitination. 1 / 1
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COPS6 affects Snail1 ubiquitination
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COPS6 affects RING-box protein 1
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COPS6 affects Lipogenesis
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COPS6 activates Lipogenesis. 1 / 1
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COPS6 affects IGHV3OR15-7
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COPS6 affects FOXO4 ubiquitination
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COPS6 affects FOXO4 protein
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COPS6 affects EPB41L4A-DT
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COPS6 affects EGFR-interacting E3 ligase CHIP
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COPS6 affects CSN7 subfamily
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COPS6 affects CSN6-CSN5 hetreodimer
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COPS6 affects CORO1A, E3_Ub_ligase, and SKP2
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COPS6 affects CDK9 ubiquitination
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eidos
"In addition , to investigate whether CSN6 controls the ubiquitination and degradation of the E3 ligase UBR5 to stabilize CDK9 , in vivo ubiquitination assays were performed and found that CSN6 increased UBR5 ubiquitination levels and decreased CDK9 ubiquitination levels in melanoma cells and 293FT cells ( Fig. 5F , G ) ."
COPS6 affects CDK9 stability
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COPS6 affects 2-NBDG uptake
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eidos
"As CSN6-FOXO4 axis impacts on the expression of Glut1 , biochemical assays that quantitates the glucose uptake ( consumption ) by assessing uptake of ( 2 - ( N - ( 7-nitrobenz-2-oxa-1 ,3 - diazol-4-yl ) amino ) -2 - deoxyglucose ( 2-NBDG ) ) , a green fluorescent glucose analog , additionally demonstrated that CSN6 knockdown inhibited 2-NBDG uptake ( Figure 5G ) , while FOXO4 knockdown increased 2-NBDG uptake ( Figure 5H ) ."
COPS4 affects CSN7 subfamily
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CHX affects COPS6
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CDK9 affects A375
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CAGTTTGTGAACAAGTTCAAT affects COPS6
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Akt signal affects COPS6
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Akt inhibitor affects COPS6
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A375 affects UBR5
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