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CYLD inhibits NFkappaB. 227 / 265
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"Our results show that reconsitituted expression of CYLD in miR-19a-replete cells only partially deactivates NF-kappaB, suggesting that CYLD might cooperate with other DUBs to switch off NF-kappaB signalling."
29050336
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"CYLD has been shown to negatively regulate the activation of NF-kappaB XREF_BIBR."
25909817
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"For instance, CYLD negatively regulates NFkappaB activation and is involved in other immune response mechanisms.39 When TSGs such as CYLD are down-regulated, excessive inflammation occurs and tumorigenic factors can be promoted.40 Conversely, TSGs that were up-regulated were more likely to be involved in cell cycle regulation, apoptosis, and cell growth, possibly as a response to cell stress in early stages of tumorigenesis."
28675510
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"Because CYLD inhibits NF-kappaB activation, it is probable that both PI3K-Akt and NF-kappaB signaling pathways are involved in CYLD regulated cell proliferation and survival."
23300340
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"In TLR mediated signaling, CYLD negatively regulates NF-kappaB signaling by cleaving K63 linked polyubiquitin chains and M1 linked polyubiquitin chains from RIPK1, TRAF2, and NEMO."
33511009
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"Interestingly, loss of CYLD causes constitutive NF-kappaB activation in developing NKT cells, which contributes to their defective IL-7 response and attenuated ICOS expression."
20224552
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"For instance, CYLD negatively regulates NFkappaB activation and is involved in other immune response mechanisms."
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"Several studies showed that the tumor suppressor CYLD inhibits NF-kB as well as the p38 MAPK pathway activation by deubiquitinating several upstream regulatory signaling molecules of these pathways, thus suppressing these signaling pathways [ xref ]."
31093340
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"This promotes the cleavage of a limited number of proteins, including A20, CYLD and RelB that negatively regulate NF-kappaB activation."
27071417
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"The lack of requirement of linear polyubiquitination in K13 induced NF-kappaB activation was further supported by our results showing that CYLD, a deubiquitylating enzyme that can cleave linear ubiquitin chains, can not block K13 induced NF-kappaB activity."
22590573
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"The tumor suppressor gene CYLD, which was recently identified as the cylindromatosis gene, has a deubiquitinating enzyme (DUB) activity and inhibits activation of the transcription factor NF-kappaB, which has key roles in inflammation, immune responses, carcinogenesis, and protection against apoptosis [XREF_BIBR]."
20414373
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"CYLD and OTULIN were not inhibiting NF-kappaB activity per se because the DUBs did not appreciably inhibit NF-kappaB activity induced by an engineered non cleavable Met1-Ub4 protein targeted to inactive XIAP."
26997266
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"Pro inflammatory insults also induce expression of the specific DUB, cylindromatosis (CYLD) which negatively regulates NF-kappaB signaling 28."
29162839
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"As a mechanism of this tumor suppressor activity , we found that a moderate increase in CYLD expression levels reduced NF-kappaB activation , which favored the differentiation of tumor epidermal cells and inhibited its proliferation ; moreover , it decreased tumor angiogenesis and inflammation ."
34201751
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"It has also been reported that optineurin is required for CYLD dependent inhibition of NF-kappaB activation in immune cells."
26527009
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"In the reporter gene assay, overexpression of CYLD attenuated NF-kappaB activity, particularly in TNF-alpha-stimulated samples (65% inhibition; P < 0.001, compared with control under TNF-alpha treatme[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18245814
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"CYLD negatively regulates NF-kappaB signaling by cleaving the K63 linked, ubiquitin chains from various NF-kappaB signaling components [XREF_BIBR]."
23434408
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"These data suggest that the mechanism of CYLD mediated NF-kappaB suppression may vary in different cell types."
20414373
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"Our findings suggest the following scenario : PKCtheta and beta are the essential kinases in a physiological signaling cascade that is necessary to counteract CYLD mediated repression of NFkappaB and NFAT transactivation."
23335970
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"T cell receptor stimulated NF-kappaB activation requires CARMA1 and is negatively regulated by the deubiquitinase CYLD."
20233721
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"Emerging evidence suggests that CYLD primarily downregulates NF-kappaB signaling by deubiquitinating NF-kappaB essential modulator ( NEMO ) and several upstream regulators like TNF receptor-associated factors 2 and 6 ( TRAF2 and TRAF6 ) and TGF-beta-activated kinase 1 ( Tak1 ) [ 23-25 ] ."
30285829
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"Similarly, CYLD is reported to suppress NF-kappaB via binding to IKKgamma and de-ubiquitination of TRAF2 and, to a less extent, TRAF6 [XREF_BIBR, XREF_BIBR]."
30471562
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"In conclusion, the present study found that high glucose significantly inhibited the expression of CYLD and activated NF-kappaB inflammatory signaling in a dose- and time dependent manner."
29259980
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"Another well-known DUB is the tumor suppressor CYLD, which inhibits NF-kappaB activation by cleaving K63 as well as linear polyubiquitin chains to inhibit IkappaK."
33643919
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"Once recruited, CYLD limits NF-kappaB activation by removing K63 linked and M1 linked poly-Ub chains on several components of complex I, including RIPK1 [XREF_BIBR, XREF_BIBR - XREF_BIBR]."
27066894
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"CYLD was recently reported to negatively regulate NF-kappaB signaling by deubiquitination, and loss of deubiquitinating activity of CYLD is correlated with tumorigenesis [XREF_BIBR - XREF_BIBR]."
20414373
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"In addition, NF-kappaB activation by CC2D1A requires the ubiquitin E2 Ubc13 and is inhibited by CYLD."
20529849
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"CYLD, a K63 specific deubiquitinase, has been shown to inhibit the NF-kappaB signaling pathway particularly by deconjugating the K63 linked polyubiquitin chains."
32901872
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"CYLD also negatively regulates NF-kappaB activation in IL-1R and TLR4 signaling through its DUB activity (Sun, 2010b)."
25175772
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"In contrast to the cylindromatosis tumor suppressor CYLD, which attenuates NF-kappaB signaling by selectively removing K63 linked polyubiquitin chains that activate IkappaB kinase, YopJ also cleaves K48 linked chains and thereby inhibits proteasomal degradation of IkappaBalpha."
16301742
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"Suppression of CYLD expression by RNA interference causes an increase in the activity of the transcription factor NF-kappaB, which is activated by TNFalpha signaling, thus inhibiting apoptosis."
17923499
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"miR-19b targets not only TNFAIP-3, but alsoother negative regulators of NF-kB signaling such as CYLD."
27019614
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"Furthermore, CYLD inhibits NF-kappaB activation by TNF and TLR/IL -1 family members."
14676304
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"Cylindromatosis (CYLD) negatively regulates the NF-kappaB signaling pathway and it is identified to be a tumor suppressor involved in familial CYLD."
29163038
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"110 Overexpression of either CYLD or A20 inhibits NF-kappaB activation by the 4-1BB agonist antibody, whereas silencing these DUBs enhances NF-kappaB activation mediated by 4-1BB costimulation in human CD8 T cells."
33436547
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"CYLD is known to inhibit the NF-kappaB signaling by removing K63 linked polyubiquitin chain from NF-kappa-B essential modulator (NEMO)."
30186311
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"It has been demonstrated that the deubiquitinating enzymes A20 and CYLD inhibit NF-kappaB signaling by targeting TRAF6 upstream of IKK, while the deubiquitinating protein DUBA inhibits type I interferon activity by targeting TRAF3."
20434986
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"Infection with Haemophilus influenzae or Eschericia coli induces CYLD expression, which down-regulates the NF-kappaB inflammatory pathway."
21455491
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"In addition to negative regulation by NF-kappaB inducible genes, NF-kappaB is negatively regulated by CYLD, a deubiquitinase that represses the activation of the IKK complex by removing K63 linked ubiquitin chains from TRAFs and NEMO XREF_BIBR, XREF_BIBR, XREF_BIBR."
22649547
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"Our previous studies demonstrated that neuronal zinc finger protein A20 and cylindromatosis (CYLD), which are important deubiquitinases that negatively regulate the NF-kappaB pathway, were required for EA to alleviate the excessive inflammatory reaction in acute ischaemic rats."
33836646
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"The deubiquitinating enzyme CYLD negatively regulates canonical NFkappaB signaling, and loss of CYLD in testicular cells leads to constitutive activation of canonical NFkappaB signaling and aberrant expression of anti-apoptotic factors, including Bcl-2, Bcl-XL, c-IAP1 and c-IAP2, in different stages of testicular cells [XREF_BIBR]."
27902973
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"Because NF-kappaB has been proven to play critical roles in the regulation of NK cell activity and cytokine production XREF_BIBR XREF_BIBR XREF_BIBR XREF_BIBR, we hypothesized that miR-362-5p might inhibit CYLD expression to induce downstream NF-kappaB signaling, thereby regulating NK cell function."
25909817
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"Results We obtained the following results : CYLD suppression enhanced proliferation , reduced apoptosis , and increased cell division of RA-FLSs and aggravated the activity of NF-kappaB in RA-FLSs ."
30285829
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"The deubiquitinating enzymes A20 and CYLD inhibit NF-kappaB signaling by targeting TRAF6 upstream of IKK, while a recent report shows that CUEDC2 inhibits IKK activity by recruiting a phosphatase PP1 and keeps IKK in an inactivated status."
21703539
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"CYLD, another DUB, is reported to limit NF-kappaB activation by removing K63- and M1 linked poly-ubiquitin chains on several complex I components (including TRAF2, NEMO and RIPK1), thereby disrupting the ubiquitin scaffold required for the recruitment and activation of the TAB2/3-TAK 1 and NEMO-IKKalpha-IKKbeta complexes [XREF_BIBR, XREF_BIBR - XREF_BIBR]."
27424290
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"The tumor suppressor CYLD antagonizes NF-kappaB and JNK signaling by disassembly of Lys63 linked ubiquitin chains synthesized in response to cytokine stimulation."
18313383
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"Initial studies revealed that CYLD negatively regulates NF-kappaB activation by different inducers, including TNF-alpha, IL-1, CD40, and PMA."
19373246
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"These observations suggest that suppression of CYLD enhances the activity of the IKK kinase and the nuclear localization of NF-kappaB transcription factors."
20832754
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"MiR-19 inhibits the expression of CYLD and induces downstream NF-kappaB."
22362744
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"Follow-up validation revealed that K. pneumoniae exploits an EGF receptor (EGFR)-PI3K-AKT-PAK4-ERK-GSK3beta signaling pathway to induce the expression of the deubiquitinase CYLD to attenuate the cytokine dependent nuclear translocation of NF-kappaB."
25971969
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"Functional assays revealed CYLD inhibits NPC cell proliferation and migration in vitro and suppresses NPC tumorigenicity and metastasis in vivo by negatively regulating the NF-kB signaling pathway."
32708712
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"CYLD inhibits tumor development mostly by preventing the activation of the NF-kappaB pathway."
25824820
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"This argues for the presence of a ternary complex of CYLD, TRIP, and TRAF2, which would block NF-kappaB activation by sequestering TRAF2 away from the TNF receptor."
14676304
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"CYLD was shown to negatively regulate NF-kappaB and MAPK activation by removing ubiquitin chains from key signalling molecules including NEMO, TRAF2, TRAF6 and RIPK1."
27561390
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"Consistent with these results, we found that ectopic expression of CYLD is sufficient to block Notch induced activation of an NFkappaB dependent reporter in HEK-293T (XREF_SUPPLEMENTARY)."
20832754
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"High expression level of CYLD reduced the nuclear translocation of NF-kappaB significantly and the IL-6 expression, which was dependent on the activation of NF-kappaB."
22362744
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"CYLD, a DUB that can cleave both K63- and linear linkages, was shown to negatively regulate NF-kappaB activation by removing K63-linkages from RIP1 XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR."
24375678
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"The tumor suppressor cylindromatosis (CYLD) inhibits the NF-kappaB pathway by deubiquinating the IKKgamma subunit, as well as TNF receptor associated factor (TRAF) 2, TRAF6, and B-Cell CLL and Lymphoma 3 (BCL3) that are required for maintaining NF-kB activity."
27422962
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"CYLD, a de-ubiquitinating enzyme, suppresses both the NF-kappaB pathway [XREF_BIBR, XREF_BIBR] and the c-Jun N-terminal kinase pathway [XREF_BIBR - XREF_BIBR]."
32892208
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"Similarly, in the gel shift mobility assay, overexpression of CYLD also inhibited binding of NF-kappaB to the DNA consensus sequence."
18245814
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"CYLD is known to inhibit canonical NF-kappaB activation through removing K63 linked polyubiquitin chains from a number of proteins involved in activation of the pathway such as TRAF2/6, Tak1, and NEMO and, thus, lead to their degradation by the proteasomal system XREF_BIBR."
32252875
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"Although CYLD has been firmly established as a DUB that targets NF-kappaB signaling factors, how CYLD negatively regulates NF-kappaB activation is not completely understood."
19373246
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"Moreover, the C-terminal domain of TRIP was shown to interact with the tumor suppressor CYLD, which negatively regulates NF-kappaB activation by TNF [6]."
17544371
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"Thus, CYLD, which is known to interact with PKC-theta, impaired the activation of PKC-theta and NF-kappaB in CD8 + T cells."
28203236
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"6-8 Effectively, CYLD normally acts to reduce the activity of NFkappaB."
26370355
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"MiR-181b (XREF_TABLE) is known to regulate CYLD 253, a deubiquitinating enzyme that negatively regulates NF-kappaB activity XREF_BIBR, XREF_BIBR."
25328909
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"Importantly, CYLD silencing resulted in heightened NF-kappaB activation under normoxic conditions to a degree that approximated that of the hypoxia induced NF-kappaB activation in control siRNA treated cells (XREF_FIG), suggesting that abrogation of CYLD expression in HPV positive cells is sufficient to recapitulate prolonged hypoxia induced NF-kappaB activation."
18977328
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"Previous studies report that CYLD negatively regulates NF-kappaB signaling by removing K63- and M1 linked polyubiquitin chains from key signaling molecules, including NF-kappaB essential modulator, tumor necrosis factor (TNF)-associated factor (TRAF) 2, TRAF6, and Receptor interacting serine/threonine protein kinase 1, in familial cylindromatosis tumors."
33149672
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"By deconjugating these K63 linked ubiquitin chains, CYLD negatively regulates NF-kappaB activation, which may contribute to its tumor suppressor function."
19373246
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"Recently, it has been reported that CYLD inhibits the activation of NF-kappaB by IL-1beta in 293T cells."
14676304
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"In mature T cells, CYLD targets TAK1 for inactivation to downregulate IKK and NF-kappaB activation [XREF_BIBR]."
21119682
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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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"Over-expressing CYLD augments antitumor activity of TRAIL by inhibiting the NF-kappaB survival signaling in lung cancer cells."
22017589
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"Using a shRNA library targeting 50 DUBs to identify candidates involved in the regulation of cancer related pathways , they demonstrated that knockdown of CYLD enhanced NF-kappaB signalling following Tumour Necrosis Factor ( TNF ) stimulation ( 108 ) ."
20073038
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"In turn, CYLD expression suppressed NF-kappaB signaling via TRAF6 and TRAF7 deubiquitylation, thus functioning as an autoregulatory feedback mechanism [38]."
20347313
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"Formation of the secondary, receptor-free cytoplasmic complex II is largely dependent on the activity of DUBs, specifically cylindromatosis (CYLD), A20 (also known as TNFAIP3) and ubiquitin thioesterase OTULIN, which destabilize complex I, abrogate NF-kappaB activation and release RIPK1 from complex I, which then forms the cytosolic complex II XREF_BIBR, XREF_BIBR."
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"Indeed, CYLD is thought to primarily inhibit basal NF-kappaB activation, whereas in most cell types A20 inhibits activation induced NF-kappaB."
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"Importantly, in these experimental models inhibition of NF-κB by CYLD was protective, which is in marked contrast to our study in listeriosis."
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"T cell co-stimulation with a 4-1BB agonist antibody triggers K63 ubiquitination of 4-1BB-associated TRAF2, which is crucial for NF-κB activation and induction of antitumor immunity. xref Conversely, the 4-1BB signaling is negatively regulated by two DUBs, CYLD and A20, which physically associate with the 4-1BB/TRAF2 complex. xref Overexpression of either CYLD or A20 inhibits NF-κB activation by the 4-1BB agonist antibody, whereas silencing these DUBs enhances NF-κB activation mediated by 4-1BB costimulation in human CD8 T cells. xref The role of K63 ubiquitination in 4-1BB-mediated CD8 T cell costimulation is further supported by the finding that CD8 effector and memory T cells expressing a dominant-negative mutant of the E3 ligase cIAP2 (cIAP2 H570A ) have attenuated 4-1BB signaling and impaired survival, demonstrated using a viral infection model. xref "
33436547
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"Consistent with this result, we also found that overexpression of CYLD did not inhibit TAK1 and TAB1 co-overexpression-induced NF-kappaB activation in a reporter assay (XREF_FIG)."
21331078
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"Depending on the cellular context CYLD has been shown to negatively regulate NF-kappaB and/or JNK signalling pathways resulting in suppression of cell proliferation and survival."
19893491
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"This is further supported by our data that the Lys-63-specific deubiquitinase CYLD inhibits NF-kappaB activation by CC2D1A."
20529849
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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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"Interestingly, the tumor suppressor CYLD, which is induced by TNFalpha and negatively regulates NF-kappaB signaling and adlican, which is involved in colon cancer progression, were both up-regulated in cartilage from patients with late-stage OA."
18576389
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"Strikingly, the CYLD and TRAF3 genetic alterations affected mutually exclusive HPV+ HNSCC tumor groups, suggesting that alterations in either TRAF3 or CYLD may function independently and sufficiently to deregulate the downstream NF-kappaB and IFN responses."
28295216
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"CYLD downregulates NF-kappaB and its primary action is by the removal of ubiquitin (ubiquitin is a regulatory protein with widespread distribution in eukaryotic cells) [XREF_BIBR]."
26114124
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"Interestingly, although loss of CYLD causes NF-kappaB activation in the CARMA1 deficient thymocytes, the CYLD deficiency fails to rescue the defect of CARMA1 knock-out mice in Treg development."
20233721
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"It is likely that CYLD and A20 inhibit NF-kappaB at different times during an inflammatory response."
21119682
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"However, recent research revealed that CYLD inhibited NF-kappaB signaling by deconjugating the polyubiquitylation of phosphorylated IkappaBalpha proteins and rendered resistance to murine hepatocyte death [XREF_BIBR]."
29259980
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"Besides , miR-186-5p was found to target CYLD lysine 63 deubiquitinase ( CYLD ) [ 41 ] , which inhibits nuclear factor kappa B ( NF-kappaB ) - dependent CCDN1 expression [ 93 ] ."
33435156
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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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"We speculate that CYLD deubiquitinase negatively regulates NF-kappaB inflammatory signaling by deconjugating the polyubiquitylation of phosphorylated IkappaBalpha, followed by inhibiting activation of NF-kappaB signaling under high glucose environments."
29259980
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"Both A20 and CYLD limit the duration of NFkappaB activation via a ubiquitin editing mechanism."
22479513
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"CYLD has been known to negatively regulate NF-kappaB activation in TCR signaling by removing K63 linked polyubiquitin chains from TAK1."
25175772
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"CYLD functions to downregulate NFkappaB signaling, in which the UPS has several roles [XREF_BIBR]."
19007433
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"K13 induced NF-kappaB activity was not blocked by CYLD, a deubiquitylating enzyme that can cleave linear and Lys63 linked ubiquitin chains."
22590573
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"9 Overexpression of CYLD significantly decreased NF-kappaB activity in BAECs; however, overexpression of a catalytically inactive mutant, CYLDdelor CYLD C/A, showed no change in NF-kappaB activity."
18245814
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"Whether CYLD inhibits the activation of NF-kappaB signaling through the deubiquitination of IkappaBalpha in high glucose conditions is unclear."
29259980
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"This deubiquitinating activity is required for CYLD inhibition of NF-kappaB activation and is likely affected by mutations found in cylindroma patients."
14676304
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"CYLD can inactivate NFkappaB signaling pathway through ubiquitination and regulate the apoptosis of hematological tumors."
33827598
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"CYLD abrogates the activation of NF-kappaB signaling via its deubiquitinating activity on multiple NF-kappaB signaling mediators, including TRAF2, TRAF6, RIP1, TAK1, NEMO, and BCL3 [XREF_BIBR - XREF_BIBR]."
24495516
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"CYLD, a K63 specific DUB, inhibits NF-kappaB signalling transmission by specifically removing K63 linked polyubiquitin chains from multiple key intermediaries, including RIP1, NEMO, and B-cell CLL and lymphoma 3 (BCL3) [XREF_BIBR - XREF_BIBR]."
25595906
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"However, the reduced binding to ubiquitin may also contribute towards its effect on CYLD dependent inhibition of NF-kappaB activation."
21408173
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"Alternatively, cylindromatosis protein (CYLD), another DUB, might partly compensate for the loss of A20 expression and prevent exaggerated NF-kappaB signalling activity in these cells under steady-state conditions."
23059429
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"Inhibition of CYLD increased the NF-kappaB activity and gemcitabine resistance in Panc1 and PSN1 cells."
24075517
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"Consistent with the results in ECs, overexpression of a catalytically inactive mutant, CYLDdel or CYLD C/A, showed no change in NF-kappaB activity, although overexpression of wild-type CYLD significan[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"CYLD Suppresses NF-kB Signaling Pathway via Inhibiting p65 Nuclear Translocation."
32708712
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"It has been reported that CYLD attenuates NF-kappaB signaling by removing lysine63 ( Lys63 ) - linked polyubiquitin chains from TRAF2 or TRAF6 , leading to programmed cell death [ 64 ] ."
30285829
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"It was observed in malignant melanoma that loss of CYLD also induces nuclear accumulation of BCL-3 and NF-kappaB activation, with the consequence of induced N-cadherin (migration) and cyclin D1 (proliferation) activity."
29344161
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"Studies conducted in cancer cell lines demonstrated that TRAF2 deubiquitylation is required for CYLD mediated inhibition of the NF-kappaB pathway."
25824820
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"These results indicate that CYLD knockout resulted in hyperactive NF-kB signaling, which could affect the stromal TME."
32708712
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"It is possible that fibulin-3 downregulation increases CYLD that in turn inhibits NF-kappaB signaling, but the mechanisms by which fibulin-3 regulates CYLD at the transcriptional level is yet unknown."
28414309
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"CYLD negatively regulates the NF-kappaB signaling pathway and osteoclast differentiation largely through antagonizing TNF receptor associated factor (TRAF)-mediated K63-linkage polyubiquitination in osteoclast precursor cells."
24961988
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"CYLD had ubiquitination function and previous studies have found that CYLD can inactivate NFkappaB signaling pathway through ubiquitination and regulate the apoptosis of hematological tumors [XREF_BIBR]."
33827598
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"CYLD suppression enhanced the production of pro inflammatory cytokines, MMPs, and RANKL by activating NF-kappaB in RA-FLSs."
30285829
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"GRA15 is able to constitutively activate NF-kappaB, but this activation leads to the expression of negative feedback regulators, such as the deubiquitinating enzymes A20 (TNFAIP3) and CYLD, which normally act to quickly down-regulate NF-kappaB signaling."
21199955
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"Inhibition of CYLD increased resistance to apoptosis by activating NF-kappaB, suggesting a mechanism through which loss of CYLD contributed to oncogenesis in lung cancer cells [XREF_BIBR]."
27738385
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"Taken together, these studies indicate that CYLD is essential to prevent spontaneous activation of NF-kappaB in peripheral T and B lymphocytes and is important for the maintenance of immune homeostasis."
21119682
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"The results established that CYLD down-regulates NF-kappaB activation by TNF-alpha."
14676304
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"As both CYLD and OTULIN negatively regulate the NF-kappaB signalling cascade, the impact of these deubiquitinases in different LUBAC dependent signalling cascades may be context dependent."
28446710
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"When transfected in cell lines, CYLD inhibits the activation of NF-kappaB and mitogen activated protein kinases stimulated by innate immune receptors, such as the Toll like receptors and TNF receptors."
17548520
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"CYLD inhibits activation of NF-kappaB by the TNFR family members CD40, XEDAR and EDAR in a manner that depends on the deubiquitinating activity of CYLD."
12917689
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"NF-kappaB reporter assays in HeLa cells transiently transfected with pCruzCYLD1 or pHATRIP showed that CYLD inhibited in a dose dependent manner TNF-alpha-mediated activation of the NF-kappaB reporter gene similar to TRIP (XREF_FIG A)."
14676304
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"We used TNFR1, CD40, and EDAR (Ectodermal Dysplasia Receptor) as controls for this experiment since NF-kappaB activation by these receptors is known to require linear polyubiquitination or is inhibited by CYLD XREF_BIBR, XREF_BIBR."
22590573
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"Thus, the normal function of CYLD is to downregulate NF-kappaB activation through its deubiquitinating activity, thereby maintaining a balance between the life and death of cells."
15196553
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"This hypothesis is further supported by our results showing that K13 induced NF-kappaB is not blocked by CYLD, a deubiquitylating enzyme that cleaves both linear and Lys63 linked ubiquitin chains XREF_BIBR, XREF_BIBR."
22590573
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"The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination."
12917691
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"Studies found that miR-362-5p reduces the expression of tumor suppressor protein CYLD, which leads to activate the NF-kB pathway to promote the proliferation, migration, and invasion of hepatocellular carcinoma cells and human breast cancer cells (Ni et al., 2015; Ni et al., 2016)."
32194406
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"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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"Moreover, transfection of p65 alone or in combination with p50 increased the 3XkappaB luciferase reporter activity to a similar extent in Cyld +/+ and Cyld -/- keratinocytes, confirming that Cyld nega[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
16713561
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"Interaction with the stroma, via ICAMs or integrins, may be amplified or perpetuated by mutations in NF-kappaB activators such as IKKepsilon, or by loss of NF-kappaB attenuators such as CYLD."
20424119
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"In summary, we have identified TRIP as interactor of CYLD and show that CYLD inhibits NF-kappaB activation by TNF-alpha."
14676304
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"Cyld -deficient mice have been generated by different groups, and these mice display a myriad of phenotypes that overall support the conclusion that CYLD inhibits IKK and NF-kappaB and contributes, at[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
19217402
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"The mechanism of Notch induced NF-kappaB activation in T-ALL involves Hes1, which transcriptionally represses CYLD (cylindromatosis), a deubiquitinase which down-regulates NF-kappaB signaling by removing the activator K63 ubiquitin chains from different elements of the NF-kappaB signalosome [XREF_BIBR]."
28561798
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"The tumor suppressor CYLD has been shown to inhibit NF-kappaB activation by binding TRAF2 and removing its ubiquitin chains, thereby preventing TRAF2 activation of the IKK complex (Brummelkamp et al.,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
21810480
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"Accordingly, overexpression of the deubiquitinase CYLD capable of disassembling K63 chains inhibited activation of TAK1 and NF-kappaB by VP16, whereas its catalytic mutant (CYLD-Mut) did not (XREF_FIG)."
20932476
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"CYLD removes Lys-63-linked ubiquitin chains from IKK signaling components, including NEMO, and thereby inhibits NF-kappaB pathway activation."
20484576
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"Three simultaneous publications demonstrated that CYLD negatively regulates NF-kappaB signaling via DUB activity."
21119682
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"These data indicate that, depending on the external signals, Cyld can negatively regulate different NF-kappaB pathways; inactivation of TRAF2 controls survival and inflammation, while inhibition of Bcl-3 controls proliferation and tumor growth."
16713561
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"miR-130b inhibited CYLD expression and activated NF-kappaB signaling."
27391066
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"These analyses revealed that the tumor suppressor CYLD, which inhibits NF-kappaB pathways at various steps, was mutated in 11% of HPV+ HNSCC (XREF_FIG, left)."
28295222
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"CYLD prevents the spontaneous activation of NF-kappaB in B lymphocytes since Cyld -/- B cells exhibit constitutive IKK and NF-kappaB activation [XREF_BIBR]."
21119682
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"It is likely that CYLD and A20 inhibit NF-κB at different times during an inflammatory response."
21119682
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"It is possible that CYLD inhibits NF-κB, not only through the regulation of TRAF6, but through the regulation of IKKγ ( xref , xref , xref )."
19201866
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"CYLD, a tumor suppressor and a target gene of NF-kappaB, negatively regulates NF-kappaB and JNK activation by removing K63 linked polyubiquitin chains from TRAF2 and TRAF6 as well as several other signaling proteins [XREF_BIBR, XREF_BIBR]."
23758787
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"As a mechanism of this tumor suppressor activity, we found that a moderate increase in CYLD expression levels reduced NF-kappaB activation, which favored the differentiation of tumor epidermal cells and inhibited its proliferation; moreover, it decreased tumor angiogenesis and inflammation."
34201751
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"Importantly, in these experimental models inhibition of NF-kappaB by CYLD was protective, which is in marked contrast to our study in listeriosis."
23825949
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"Treatment of BAECs with TNF-alpha (10 ng/ml) for 12 hours significantly up-regulated NF-kappaB activity, whereas overexpression of CYLD significantly attenuated NF-kappaB activity, particularly in TNF[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18245814
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"CYLD inhibits NF-kB, a cellular proliferation switch in many cancers ( xref )."
30933315
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"As expected, CYLD expression in CYLD KO cells reduced baseline NF-kappaB activity to the same level as in WT cells (XREF_FIG C)."
27591049
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"As CYLD could not inhibit NF-kappaB activation in H486R expressing cells, we next examined whether CYLD can deubiquitinate RIP in presence of H486R mutant."
21408173
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"Taken together, these data demonstrated that the levels of both CYLD and NF-kappaB mRNAs accumulated in HSG cells during 24 h after TNF-alpha stimulation, although the NF-kappaB activity in the cells was at least negatively regulated by CYLD."
18497946
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"The deubiquitinating enzyme CYLD cleaves K63 linked polyubiquitin chains from specific substrates, including tumor necrosis factor receptor associated factors (TRAF)-2, TRAF6, transforming growth factor beta activated kinase 1 (TAK1), B cell lymphoma 3 (BCL3), STAT3, nuclear factor kappa B essential modulator (NEMO), and retinoic acid inducible gene 1 (RIG-1), and negatively regulates the activation of NF-kappaB, MAPKs, and type I IFN production."
26834734
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"Adding complexity to the issue, recent studies showed that a deubiquitinating enzyme, CYLD, a known negative regulator of NF-kappaB activity, interacts with p62 as well as TRAF6 to dysregulate NF-kappaB activity under certain conditions."
19201866
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"It is possible that CYLD inhibits NF-kappaB, not only through the regulation of TRAF6, but through the regulation of IKKgamma."
19201866
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"CYLD is known to negatively regulate NF-kappaB signaling, and is closely involved in the apoptosis of cancer cells [29]."
24075517
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"These results suggest that the inhibitory effect of CYLD on NF-kappaB activity is attributable to its deubiquitinating action through the deubiquitination of TRAF2.In rat smooth muscle cells (A7r5), o[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18245814
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"One example is the deubiquitinase (DUB) CYLD, which inhibits NF-kappaB activation by cleaving K63 linked and linear ubiquitin chains from several signaling components."
26260210
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"161 Cylindromatosis (CYLD) has been shown to inhibit NFkappaB activation 160 and more recent results indicate that this inhibition might be mediated via the ability of CYLD to hydrolyze unanchored polyubiquitin chains and thus inhibit TAK1 and IKK activation."
22223213
eidos
"CYLD can inhibit NF-kB signaling via deubiquitinating TRAF2 [ 18 ] ."
32708712
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"Perhaps differential NF-kappaB regulation may explain2 those discrepancies, because A20 terminates NF-kappaB signaling, whereas CYLD prevents spontaneous NF-kappaB activation."
28842469
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"CYLD Reduces Activation of PKC-theta and Impairs NF-kappaB Activation in CD8 + T Cells."
28203236
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"In this study, we investigated the distinct roles of miR-19a on cell apoptosis initiated by OS and identified the possible mechanism : restoration of CYLD repression mediated NF-kappaB transactivation."
29050336
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"Like TRAF3, CYLD inhibits NF-kappaB pathways at various steps including, binding, deubiquitinating, and inhibiting the NF-kappaB essential modulator (NEMO)."
28295222
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"In a similar study, CYLD was shown to negatively regulate NF-kappaB activation and lung inflammation in mice infected with non typeable Haemophilus influenzae 22."
18535581
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"These data further confirmed knockout of CYLD induces NF-kB hyperactivity."
32708712
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"Like TRAF3, CYLD inhibits NF-kappaB pathways at various steps including binding, deubiquitinating, and inhibiting the NF-kB essential modulator, NEMO."
28295222
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"These results revealed that high glucose mediated activation of NF-kappaB inflammatory signaling was blunted by overexpression of CLYD, suggesting that CYLD deubiquitinase negatively regulated NF-kappaB inflammatory signaling in GMCs."
29259980
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"Similarly , de-ubiquitinating enzyme cylindromatosis ( CYLD ) inhibits NF-kappaB signaling via de-ubiquitination and inactivation of TNFR-associated factor 2 ( TRAF2 ) and TRAF6 [ 18,19 ] ; de-ubiquitinating protease A20 inhibits NF-kappaB activation induced by Toll-like receptor 4 ( TLR4 ) via removing K63-linked polyubiquitin chains of TRAF6 [ 20 ] ."
27164085
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"This provides evidence that both the deubiquitinating activity and the central domain, which interacts with TRIP, are required for CYLD repression of NF-kappaB activation."
14676304
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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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"This downregulation was observed with other NF-kappaB activators such as TRAF6 and partially rescued by NF-kappaB downregulators such as CYLD."
26134525
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"CYLD overexpression inhibits, whereas RNAi against CYLD enhances, the activation of TAK1, IKK, and JNK. -deficient mice have been generated by different groups, and these mice display a myriad of phen[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
19217402
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"In the presence of WT CyldNF-kappaB transcriptionally induces CYLD, which in turn inhibits NF-kappaB activation, thereby forming a self regulated signaling loop."
27478875
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"CYLD and A20 negatively regulate the NF-kappaB pathway [XREF_BIBR]."
21951562
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"This suppression of CYLD promoted ubiquitin conjugation of NF-kappaB signaling pathway components and induction of an aggressive phenotype of glioma cells both in vitro and in vivo."
23006329
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"The involvement of Ubc13 in this pathway suggests that Lys-63 polyubiquitination is involved in IKK activation by CC2D1A. This is further supported by our data that the Lys-63-specific deubiquitinase CYLD inhibits NF-κB activation by CC2D1A."
20529849
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"Consequently, CYLD inhibits the activation of the transcription factor NF-kappaB, which plays an important role for immune responses."
23825949
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"To date, the majority of characterized CYLD targets are involved in the signaling transduction mediating NF-kappaB activation."
22406061
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"Expression of CYLD suppressed the NFkappaB activation by TRAF2 or TRAF6 in a dose dependent manner as described previously [15-17], whereas it had no effect on Tax induced NFkappaB activation."
17418100
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"By negatively regulating NF-kappaB activation, CYLD limits the inflammatory response during infections, thus minimizing tissue damage."
25824820
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"First, CYLD inhibits NF-kappaB signaling by deubiquitinating NF-kappaB-positive regulators, such as TAK1 (TGF-beta-activated Kinase 1), TRAF2 and NEMO and IKKgamma."
27383048
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"In mammalian systems, Cyld is a NF-kappaB target [XREF_BIBR] and represses NF-kappaB in a negative feedback mechanism by its action on IKKgamma and adaptor molecules such as TRAF2 and TRAF6 [XREF_BIBR]."
24993778
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"NTHi induced CYLD, in turn, negatively regulates NTHi induced NF-kappaB activation through deubiquitinating TRAF6 and 7 and down-regulates inflammation."
17925880
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"Mutations in the CYLD gene that encodes for a tumor suppressor protein negatively regulate NF-kappaB activation."
21170083
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"CYLD can inhibit NF-kB signaling via deubiquitinating TRAF2 [XREF_BIBR]."
32708712
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"While A20 acts as a negative feedback mechanism to NF-kappaB stimulation, CYLD is thought to suppress basal NF-kappaB activation."
26732666
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"We found that CYLD reduced and activated increased NF-kappaB in cholesteatoma epithelium in comparison to RA skin."
20414373
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"CYLD has deubiquitinating enzyme activity and inhibits the activation of transcription factor NF-kappaB."
16900776
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"CYLD negatively regulates activation of the cell-survival effector NF-kappaB, a finding that links its genetic characterization as a tumor suppressor to a cellular phenotype (Ikeda and Dikic, 2006)."
18313383
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"CYLD Impairs Production of Cytokines, ROS, and NO and Reduces Activation of NF-kappaB, ERK1/2, and p38MAPK in Lm Infected BMDM."
26834734
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"CYLD and TNFAIP3 and A20 negatively regulate the NFkappaB pathway by removing ubiquitin chains from multiple signaling molecules including TRAFs and RIP."
19615732
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"EAC inhibited constitutively activated and inducible NF-kappaB in both its DNA-binding activity and transcriptional activity."
17316946
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"A deficiency of CYLD causes constitutive NF-kB activation and enhanced TGF-b signaling, which increases the frequency of Treg cells in peripheral lymphoid organs and promotes Treg cell differentiation in vitro (149, 150)."
31681337
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"XREF_BIBR, XREF_BIBR In support of the role of CYLD and A20 in NF-kappaB regulation, recent genetic evidence and the mutation analysis show that knockout of CYLD in mice or mutations on CYLD and A20 genes in patients causes the hyperactivation of NF-kappaB resulting in tumor susceptibility or tumor formation."
20081374
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"The CYLD knockdown also led to the degradation of the NF-kappaB inhibitor, IkappaB-alpha, resulting in enhanced NF-kappaB activity in HCC cells."
21109933
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"Therefore, loss of CYLD leads to enhanced activation of NFkappaB in response to many immunological and inflammatory signals."
19037995
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"CYLD Inhibits TNF-alpha-mediated NF-kappaB Activation."
14676304
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"In fact, in vitro infection of IFN-gamma-stimulated BMDMs demonstrated that CYLD inhibited activity of NF-kappaB resulting in reduced IL-6 production, ROS synthesis, and bacterial killing, which were all dependent on NF-kappaB (XREF_FIG)."
23825949
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"Furthermore, reduction of CYLD expression by RNA interference enhances the activation of NF-kappaB and protects cells from TNFalpha induced apoptosis."
15196553
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"CYLD inhibits NF-kB , a cellular proliferation switch in many cancers ( 34 ) ."
30933315
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"revealed that the deubiquitinase Cylindromatosis (CYLD) inhibits NF-kappaB signaling and downregulates the IMD response."
32656090
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"Alternatively, if NEMO ubiquitinylation positively regulates NF-kB signaling, then CYLD expression should decrease RIP2 's activation of NF-kB."
15620648
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"Optineurin is essential for CYLD mediated inhibition of NF-kappaB activation."
21408173
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"43 CYLD negatively regulates NFkappaB by removing K63 linked ubiquitin chains from TRAF2, TRAF6, and IKBKG."
26370355
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"Conversely, CYLD, a human DUB that negatively regulates the NF-kB pathway, is specific for K63 based Ub chains."
24854014
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"In order to verify whether NF-kappaB signaling is negatively regulated by CYLD in Panc1 and PSN1 cells, the NF-kappaB activity was measured by a luciferase assay."
24075517
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"CYLD negatively regulates NF-kappaB activation by removing lysine 63 linked ubiquitin chains from TRAF2/6, NEMO and BCL3, and loss of CYLD leads to hyper-activation of NF-kappaB signalling and an increased susceptibility to cutaneous tumour formation in mouse knockout models [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
25565632
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"CYLD, a tumor suppressor gene, has deubiquitinating enzyme activity and inhibits the activation of transcription factor NF-kappaB."
18497946
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"CYLD acts to downregulate NFkappaB signaling by removing these activating Lys63 linked UBIQ chains [XREF_BIBR]."
19007433
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"CYLD downregulates the NF-kappaB activation pathway by hydrolyzing K63 linked ubiquitin chains [XREF_BIBR, XREF_BIBR]."
32403254
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"Whereas CYLD prevents spontaneous activation of NF-kappaB, A20 is essential to terminate NF-kappaB signaling in a negative feedback loop [XREF_BIBR]."
21119682
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"Maybe there are two kinds of inhibition mechanism in the body : (1) A20, CYLD and IkappaBalpha, encoding by target genes of NF-kappaB, inhibit NF-kappaB activation in the feedback manner [32]; (2) NUM[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18299187
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"ELISA confirmed that the upregulation of CYLD inhibited NF-kappaB activity; however, the co-transfection of sh-LINC01260 partly reversed the inhibition."
33116647
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"Functional assays with CYLD transfected cell lines revealed that CYLD expression decreased NF-kappaB activity."
16774947
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"Similarly, de-ubiquitinating enzyme cylindromatosis (CYLD) inhibits NF-kappaB signaling via de-ubiquitination and inactivation of TNFR associated factor 2 (TRAF2) and TRAF6 [XREF_BIBR, XREF_BIBR]; de-ubiquitinating protease A20 inhibits NF-kappaB activation induced by Toll like receptor 4 (TLR4) via removing K63 linked polyubiquitin chains of TRAF6 [XREF_BIBR]."
27164085
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"Reduced or absent CYLD activity allows prolonged NFkappaB signaling, increases resistance to apoptosis and hence could lead to tumor formation [XREF_BIBR]."
19007433
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"Furthermore, since CYLD is also a negative regulator of NF-kappaB, increased levels of CYLD in the absence of caspase-8 might reduce the activation of NF-kappaB which is critical for the development of embryonic vasculature."
27984721
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"For example, p62 (also known as sequestosome 1) recruits CYLD to ubiquitinated TRAF6 [XREF_BIBR, XREF_BIBR] and facilitates CYLD inhibition of NF-kappaB activation by receptor activator of NF-kappaB (RANK) [XREF_BIBR]."
18775672
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"The MALT1 (mucosa associated lymphoid tissue lymphoma translocation 1) subunit is the active signaling component of the CBM complex and features protease activity that cleaves and inactivates inhibitors of the NF-kappaB signaling pathway such as TNFAIP3 and A20, CYLD, and RELB or the BCL10 protein, indirectly activating NF-kappaB signaling."
23238016
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"The finding that the increased NF-kappaB activity is not inhibited by over-expressed CYLD prompted us to investigate whether loss of optineurin affects levels of ubiquitinated RIP."
21408173
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"XREF_BIBR Suppression of CYLD by miR-182 promoted ubiquitin conjugation of NFkappaB signaling components and led to sustained NFkappaB activation."
26273328
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"Consistently, Knockdown of CYLD rescued the decreased activation of NF-kappaB (XREF_FIG)."
27680285
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"In the absence of PrP, CYLD is free to de-ubiquintnate RIP1 and TRAF2, reducing NF-kappaB activation."
28900035
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"These analyses revealed that the tumor suppressor CYLD, which inhibits NF-kappaB pathways at various steps, was mutated in 11% of HPV positive HNSCCs."
28295222
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"Two deubiquitinases, A20 and CYLD, negatively regulate NF-kappaB activation."
21113390
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"The tumour repressor protein CYLD, a DUB, has previously been shown to suppress potentially oncogenic NF-kappaB signalling [XREF_BIBR - XREF_BIBR]."
25565632