IndraLab

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CYLD activates NFkappaB. 77 / 84
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"Conversely, Tax inactivates multiple DUBs that oppose NF-kappaB activation including A20 and CYLD [XREF_BIBR]."
25341660
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"CYLD reduced IL-6, ROS production and killing of Lm in Listeria infected macrophages by impairing NF-kappaB activation."
23825949
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"Contrary to the widespread belief that CYLD is an absolute tumor suppressor, CYLD initiates and terminates NF-kappaB activity by alternately using its oncoprotein and tumor suppressor activities, respectively."
35958947
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"However, subsequent studies have indicated that although CYLD targets NF-kappaB signaling factors, its function may depend on the cell type and stimulating receptor [XREF_BIBR]."
29259980
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"As expected, CYLD knockdown by the two CYLD specific siRNAs significantly increased NF-kappaB reporter luciferase activity and the expression levels of the eight NF-kappaB target genes."
24495516
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"Intriguingly, LEF1 depletion mediated CYLD upregulation was sufficient to negatively modulate NF-kappaB signaling pathway in MM cells."
34269120
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"CYLD deficiency promotes constitutive NF-kappaB activity in thymocytes and peripheral T cells, and is associated with enhanced T reg cell frequencies."
28842469
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"It is possible that the negative regulation of NF-kappaB mediated by CYLD contributes to its tumour suppression function given the increasingly recognized role for NF-kappaB in cancer advancement."
27597804
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"Wild-type but not the mutant CYLD strongly inhibited NF-kappaB activation by CC2D1A, whereas RNA interference of CYLD enhanced NF-kappaB activation by CC2D1A (XREF_FIG C)."
20529849
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"A recent study demonstrated that IKBKE but not IKKalpha and beta phosphorylates CYLD XREF_BIBR, which is a deubiquitinase of several NF-kappaB regulators, including TRAF2, TRAF6, and NEMO, to activate the NF-kappaB pathway XREF_BIBR - XREF_BIBR."
23691078
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"CYLD silencing activates NF-κB to enhance HIV replication in Jurkat cells in vitro [ xref ]."
39158695
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"Importantly, this effect is blocked by concurrent inhibition of CYLD, suggesting that miR-181b-1 regulates NF-kappaB through CYLD."
20797623
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"These assumptions are strengthened by our observations which show that both inhibition of NF-κB activation by CYLD and association of CYLD with RIP are dependent on optineurin."
21408173
eidos
"Numerous studies in vitro and in vivo have validated that CYLD mediates NF-kappaB activation by deubiquitinating TRAF2 , TRAF6 , and NEMO , making it an important regulator in the adaptive immune response ."
30285829
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"Briefly, complex I activates the NF-kB pathway to promote cell survival.Moreover, the formation of new complexes, complex IIa or complex Iib, are induced when RIPK1 is deubiquitinated by the cylindromatosis enzymes (CYLD), while A20, RIPK1, and TRADD are separated from TNFR1 [145,146,147]."
35682876
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"These miR then directly target the tumor suppressor genes, phosphatase and tensin homolog (PTEN) and cylindomatosis (CYLD), thereby promote NF-kappaB activity which is required to maintain the transformed state [XREF_BIBR]."
22210182
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"Although comparable CYLD mRNA levels were present in both tumor and normal tissue, direct binding of miR-182 to 3′UTR of CYLD activated NF-κB in tumor cells."
25220353
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"The inhibition of NF-kB activation by CYLD is mediated, at least in part, by the deubiquitination and inactivation of TRAF2 and, to a lesser extent, TRAF6 [ xref ]."
18687060
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"As further validation, we assessed whether CYLD phosphorylation modulates NF-kappaB activity in the context of transformation."
19481526
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"Further examination showed that phosphorylation of CYLD at S418 decreases its deubiquitinase activity and increases NF-kappaB activation."
19481526
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"However, Treg development is not rescued in CARMA1/CYLD-double deficient mice, where the lack of the deubiquitinase CYLD activates NF-κB through TAK1/IKK."
22659217
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"Mutations in TRAF3 or CYLD Activate NF-kappaB Signaling in HPV Positive HNSCC."
28295222
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"In addition, NF-kappaB deubiquitinases CYLD and A20, which negatively regulate canonical NF-kappaB signaling, can induce NF-kappaB downstream of the BCR in miR-17 ~ 92 overexpressing B cells, and thus, have also been proposed as targets of oncomiR-1, [XREF_BIBR]."
28694140
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"It plays a role in numerous signalling pathways, for example it has been shown to phosphorylate CYLD, which in turn activates the NF-kappaB pathway via deubiquitination of several NF-kappaB regulator proteins."
32324216
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"The tumor suppressor, CYLD, inhibits NF-kappaB activation in a deubiquitinase dependent manner, by removing K63 linked ubiquitin chains from a variety of signaling proteins, including TRAF2, TRAF6, and RIP1 in T cells and other immune cells XREF_BIBR."
26240016
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"71 The gene CYLD is mutated in familial cylindromatosis, an autosomal dominant disease characterized by benign tumors derived from cells of skin appendages 72 and thus it can be considered as a TS, CYLD inhibits tumor cell proliferation by blocking BCL-3-dependent NF-kappaB signaling."
25190145
eidos
"In conclusion , the present study suggests that colon cancer may be inhibited through miR-181b downregulation to promote CYLD expression , which in turn attenuates NF-kappaB activity ."
32901872
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"Since optineurin knockdown cells accumulate higher levels of ubiquitinated RIP and CYLD fails to abolish NF-kappaB activation, it is plausible that optineurin is required for deubiquitination of RIP by CYLD."
21408173
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"Of the 128 screened siRNA pools, 15 matched these criteria including those targeting the known negative regulators of NF-kappaB signalling CYLD and A20."
22212761
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"These assumptions are strengthened by our observations which show that both inhibition of NF-kappaB activation by CYLD and association of CYLD with RIP are dependent on optineurin."
21408173
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"Because gammaTE inhibits TAK1 phosphorylation (XREF_FIG) and overexpression of CYLD or A20 blocks NF-kappaB activation in cells and animals, we investigated whether gammaTE has any impact on these NF-kappaB negative regulators."
26002975
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"In contrast, when the NF-kappaB pathway is overactive, as in mice expressing the constitutively activated IkappaB kinase in hematopoietic cells or mice deficient in the negative regulator of NF-kappaB signalling CYLD, NKT cellsdevelop but these cells fail to mature and to populate the periphery 61."
29142275
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"XREF_BIBR, XREF_BIBR Activated IKEKE also regulates CYLD, 8 which is a deubiquitinase of several nuclear factor (NF)-kappaB regulators, including tumor necrosis factor receptor associated factor 2, 6 (TRAF2, TRAF6) and NEMO (IKK-gamma), to activate the canonical NF-kappaB pathway."
22330135
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"Because CYLD modulates the NF-kappaB pathway, a crucial mediator of inflammation, 15-18 these data suggest that CYLD may regulate vascular remodeling.Previous studies have suggested that the DUB activ[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18245814
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"Because the genes encoding these two proteins are regulated by NF-kappaB, this result further supported the conclusion that CYLD deficiency causes the constitutive activation of NF-kappaB."
17548520
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"The inhibition of NF-kappaB activation by CYLD is mediated, at least in part, by the deubiquitination and inactivation of TRAF2 and, to a lesser extent, TRAF6."
18245814
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"CYLD deficiency promotes the activation of NF-kappaB and induction of anti-apoptotic genes in germ cells."
22435550
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"However, in other studies, CYLD deficiency did not affect peripheral B cell numbers, but increased NF-kappaB activation upon stimulation."
24917867
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"XREF_BIBR, XREF_BIBR Similarly, in a hepatocytespecific cylindromatosis deficient (CYLD Deltahep) mouse model, which typically has increased hepatocyte TAK1 and NF-kappaB activation, TAK1 deletion decreased HCC development."
30809789
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"Biochemical studies of CYLD -/- peripheral T cells and B cells showed constitutively phosphorylated IKKbeta and activated NF-kappaB [XREF_BIBR, XREF_BIBR]."
23474202
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"However, constitutive phosphorylation of CYLD by IKK inactivates CYLD in HTLV-1-induced leukemia to promote heightened NF-kappaB activation."
22435550
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"63 Although how CYLD regulates Bcl3 expression is unclear, one possibility is suggested by the finding that the CYLD ex7/8 B cells display constitutive NF-kappaB activity and overexpress several NF-kappaB target genes, including RelB, NF-kappaB2, and TRAF2."
19373246
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"CYLD restricts inflammation by inhibiting NFkappaB activation [XREF_BIBR], yet it can induce innate immune responses by stabilizing STING, a cytosolic DNA sensor and a major regulator of type I interferon signaling, via its deubiquitination on K48 linked chains [XREF_BIBR]."
| PMC
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"Our study supported the involvement of six candidate genes in susceptibility to psoriasis : SCL12A8, which belongs to the solute carrier gene family; FLG and TGM5, which are involved in epidermal differentiation; CARD15 and CYLD, which modulate the transcription factor NF-kB; and IL1RN, which encodes an IL receptor antagonist."
19554025
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"That is, inhibition of endogenous CYLD expression by CYLD siRNA in C33A cells (XREF_FIG) abrogated the hypoxia induced NF-kappaB activation associated with ectopic E6 expression (XREF_FIG)."
18977328
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"The CYLD deficiency causes marked activation of NF-kappaB in germ cells, which is associated with heightened expression of anti-apoptotic genes, such as Bcl-2."
19373246
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"Although comparable CYLD mRNA levels were present in both tumor and normal tissue, direct binding of miR-182 to 3 ' UTR of CYLD activated NF-kappaB in tumor cells."
25220353
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"Although CYLD suppression was shown to decrease the induction of NF-kappaB, its role in activating cell death with K. pneumoniae infection was not established."
28125817
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"On the other hand, mice that express overactive NF-kappaB or lack the negative regulator of NF-kappaB signaling CYLD, develop NKT cells but fail to mature and populate the lymphoid organs and peripheral tissues."
29312339
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"Deubiquitinases A20 and Cezanne, but not CYLD, are induced by NF-kappaB to negatively regulate TAK1 and NF-kappaB activity by removing K63 polyubiquitin chains [XREF_BIBR]."
24443058
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"In support of this view, MALT1 proteolysis of the inhibitory deubiquitinases A20 and CYLD potentiates NF-kappaB and JNK, respectively [XREF_BIBR, XREF_BIBR], while cleavage of the RNase Regnase-1 prolongs mRNA stability of T cell effector genes [XREF_BIBR]."
25965667
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"Previous reports have demonstrated that Notch signal represses the expression of CYLD that negatively regulates NF-kappaB activation in macrophages XREF_BIBR."
27680285
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"As displayed in Figure xref F, Cyld −/− BMDM showed enhanced activation of NF-κB as indicated by increased phosporylation of p65 and IκB-α."
26834734
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"MALT1-dependent cleavage of CYLD promotes NF-kappaB signaling and growth of aggressive B-cell receptor-dependent lymphomas."
36922488
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"One study demonstrated that Cyld is targeted for degradation by HPV (human papillomavirus) E6 virus, to prolong NF-kappaB activation following hypoxia [XREF_BIBR]."
24993778
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"Ablation of CYLD, NFKBIA, TRAF2, or TRAF3 induces hyperactivation of the canonical and/or noncanonical NF-kappaB pathways and subsequently diminishes CC-122-induced apoptosis in 5 of 6 DLBCL cell lines."
33847741
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"In addition to activation via PI3K-Akt (described above), it has been proposed in T-ALL that the Notch gene Hes1 suppresses the expression of the tumor suppressor Cyld, an inhibitor of NF-kB, leading to NF-kB activation and enhanced T-ALL cell survival."
27959635
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"However, Treg development is not rescued in CARMA1 and CYLD-double deficient mice, where the lack of the deubiquitinase CYLD activates NF-kappaB through TAK1 and IKK."
22659217
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"Furthermore, Cyld inhibits tumor cell proliferation by blocking Bcl-3-dependent NF-kappaB signaling."
18574737
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"The inhibition of NF-kB activation by CYLD is mediated, at least in part, by the deubiquitination and inactivation of TRAF2 and, to a lesser extent, TRAF6 [XREF_BIBR]."
18687060
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"miR-181b (activated by STAT3), has recently been identified as involved in a positive feedback loop by inhibiting CYLD (negative regulator of NF-kappaB), which in turn causes increased NF-kappaB, that completes the loop by leading to STAT3 activation."
22114691
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"These researchers found that the familial cylindromatosis tumour suppressor gene (CYLD), previously of unknown function, could enhance the activation of the transcription factor NF-kappaB, leading to increased resistance to apoptosis."
14585643
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"Importantly, the inhibition of NF-kappaB activity by an IKK inhibitor decreased p-STAT1 to equally low levels in both Lm infected WT and Cyld -/- BMDM indicating that the activation of STAT1 was dependent on the augmented Listeria induced NF-kappaB activation."
26834734
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"Although A20 and CYLD target the same set of NF-kappaB signaling factors, knockout mouse studies indicate nonredundant roles."
18775672
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"Cyld inhibits tumor cell proliferation by blocking Bcl-3-dependent NFkappaB signaling."
30676842
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"We show that CYLD deficiency causes constitutive NF-kappaB activation in thymocytes, which is associated with enhanced frequency of Treg cells."
20233721
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"In line with this, it was also reported that hypoxia could promote an E6-dependent ubiquitylation and degradation of CYLD in HPV-infected cells, activating in turn the proinflammatory transcription factor NF-κB [ xref ]."
31208103
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"A major challenge in future studies is to show how ubiquitination of the CYLD targets regulates the NF-kappaB signaling."
19373246
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"In the GCB subtype, CYLD and UBD which activate NF-kappaB were downregulated in CXCR4 + compared to CXCR4 - DLBCL patients."
25704881
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"Both A20 and CYLD are direct transcriptional targets of NF-kappaB and, as such, are rapidly induced upon NF-kappaB activation, thereby providing essential feedback mechanisms promoting the cessation of the NF-kappaB response."
28829404
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"CYLD deficiency causes spontaneous IKK and NF-kappaB activation, associated with aberrant T cell activation and development of intestinal inflammation."
33436547
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"The inhibition of NF-kappaB activation by CYLD is mediated, at least in part, by the deubiquitination and inactivation of TNFR associated factor 2 (TRAF2) and, to a lesser extent, TRAF6."
12917689
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"If NEMO ubiquitinylation negatively regulates NF-kB signaling, then CYLD expression should enhance RIP2 's activation of NF-kB."
15620648
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"Other transcripts that are up-regulated in the dorsal group have a role during signal transduction : APC negatively regulates Wnt signaling XREF_BIBR, MACF1 positively regulates Wnt signaling XREF_BIBR, CYLD and MAST2 positively regulates NF-kappaB pathway XREF_BIBR."
23613853
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"[77] R. Massoumi, K. Chmielarska, K. Hennecke, A. Pfeifer, and R. Fassler, Cyld inhibits tumor cell proliferation by blocking Bcl-3-dependent NF-kappaB signaling."
18574737
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"Optineurin is essential both for inhibition of TNFα-induced NF-κB activation by CYLD and its association with RIP."
21408173
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"Lack of CYLD in cells would elevate NF-kappaB activation, which likely contributes to tumor development."
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