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TNFAIP3 inhibits NFkappaB. 142 / 157
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"XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR Other genes negatively regulate NF-kappaB activation, such as the TNF alpha induced protein 3 (TNFAIP3; A20), a ubiquitin editing enzyme which downregulates NF-kappaB signaling when binding TNFAIP3 interacting proteins 1 and 2 (TNIP1 and TNIP2, respectively)."
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"Further studies showed that lncRNA UCA1 could promote the expression of A20 by inhibitingmiR125a , and up-regulated A20 decreased the activity of NF-kappaB through its ubiquitin editing function ."
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"A20 inhibits NF-kappaB activation indirectly through interference with proteins that transduce the signal from the TNF receptor complex to activate the IkappaB kinase ( IKK ) complex ."
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"A20 inhibits NF-kappaB activity indirectly through interference with proteins mediating the signal from the TNF receptor complex to the IKK complex ( Lork et al ., 2017 ) ."
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"TNFAIP3 (A20), as a deubiquitinating protein, can deregulate NF-kappaB-dependent gene expression and inhibit NF-kappaB function by deubiquitinating specific NF-kappaB signaling molecules [XREF_BIBR, XREF_BIBR]."
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"Since these signaling cascades end up activating NF-kappaB and thus prompting inflammation , the expression of TNFAIP3 , in turn , leads to the suppression of NF-kappaB , inhibiting inflammatory reactions initiated by these signaling cascades ."
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"Consequently, TNFAIP3 disruption in MZL causes supraphysiological activation of NF-kappaB signaling."
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"Among the cell lines studied, LY3 carries an activating mutation in CARD11 [XREF_BIBR] (XREF_SUPPLEMENTARY); LY3, LY10, U2932 (ABC) along with LY8, VAL, and SUDHL2 (GCB) carry inactivating mutations or hemizygous deletion in TNFAIP3 (A20), which negatively regulates NFkappaB activity."
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"In addition A20 can also inhibit NF-κB by interacting with and sequestering Nemo (IKKγ), thus impeding IKKβ activation without requiring the DUB and E3-ubiquitin ligase activities of A20 ( xref – xref )."
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"However , TNFAIP3 ( A20 ) prevents NF-kappaB activation by inactivating RIPK2 ( 113 , 114 ) ."
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"The A20-dependent inhibition of NF-κB requires a number of A20-associating proteins called ABINs (A20-binding inhibitor of NF-κB activation)."
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"whether and how ABIN1 and A20 cooperatively interact to inhibit NFkappaB activation as in TNF signaling ) is less well defined ; however , ABIN1 can inhibit IL-17 signaling independent of A20 ( Cruz et al. 2017 ) ."
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"Recently, A20 (TNFAIP3), a cytoplasmic zinc finger protein, was shown to inhibit NF-kappaB activation in the TNFR and TLR pathways."
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"We cannot exclude, however, that an additional antiinflammatory effect of NF-κB inhibition by A20 also contributes to its protective function."
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"Because A20 inhibits NF-κB, lower expression of this protein may reduce its NF-κB inhibitory effects, and NF-κB may be upregulated [ xref , xref ]."
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"In the early 2000s, the mechanism of how A20 inhibited NF-κB was still poorly understood."
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"A20 is strongly induced upon TNF signaling , and potently inhibits NFkappaB signaling [ 208 ] ."
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"Moreover , the negative feedback loop of suppressing NF-kappaB and associated inflammatory signaling by A20 is not functional in aged HSC ."
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"Since numerous inflammatory stimuli via cognate receptors converge to activate NF-kappaB , we examined whether SKBHT suppresses the activity of NF-kappaB by inducing TNFAIP3 , an ubiquitin-modulating protein that suppresses proinflammatory signaling originating from receptors for IL-1beta , TNF-alpha , or LPS [ 31 ] ."
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"Since TNFAIP3 inhibits TLR4 signaling and consequently suppresses NF-kappaB activation , we examined whether the expression of TNFAIP3 by SKBHT results in the suppression of NF-kappaB activity ."
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"TNFAIP3 is upregulated by TNFa or other cytokines and inhibits NF-kB activation."
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"TNFAIP3 can attenuate the NF-kB activity triggered by signaling from TNF and Toll like receptors,74 and is implicated 374 J. K. WIENCKE ET AL.in several autoimmune diseases."
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"Therefore, both these ubiquitin ligases are required by TNFAIP3 to inactivate NFkappaB signaling 21."
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"Indeed , TNFAIP3 interferes with TLR ( Toll-like receptors ) and NOD2 ( nucleotide-binding oligomerization domain 2 ) signaling pathways to limit NF-kappaB activation and pro-inflammatory cytokine production [ 41,42 ] , which may help infected IECs to limit the pro-inflammatory responses induced by AIEC infection [ 8,9 ] ."
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"Since it is expressed strongly in the gastrointestinal tract, its deficiency as observed by us is likely to affect multiple pathways in the colon including TNFAIP3 mediated NFkappaB inhibition 48."
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"A20 is prematurely upregulated by measles virus P protein thus preventing NFkappaB activation [ 27 ] ."
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"Accordingly, with higher UBE2L3, NF-κB could be less inhibited by TNFAIP3."
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"Therefore we hypothesize that decreased expression of TNFAIP3 along with its partner molecules ITCH, RNF11 and Tax1BP1 leads to uncontrolled activation of NFkappaB."
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"Consistent with this , our results show that SKBHT suppresses NF-kappaB by inducing the expression of TNFAIP3 ."
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"XREF_BIBR TNFAIP3 appears to mediate inhibition of the NF-kappaB pathway also via direct binding of ubiquitin chains on IKK and TNFR1, resulting in non catalytic interference with their signaling function."
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"IκBα and A20 both inhibit NF-κB, but mathematical modeling of the TNFα pathway revealed that IκBα restricts activation of the first phase of NF-κB activation, whereas A20 controls the second phase ( xref )."
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"It also has been suggested that A20 inhibits NF-κB in T cells by removing K63 ubiquitin chains from MALT1 xref , xref ."
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"While the binding of RIP to NEMO may initiate the activation of the IKK complex by TNF, the binding of A20 to NEMO is likely to contribute to the inhibition of NF-κB by A20."
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"As TNFAIP3 inhibits NF-kappaB activation and IEC death, expression of TNFAIP3 in IEC may provide an avenue to inhibit IEC NF-kappaB activation without inducing IEC death and inflammation."
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"For example, the deubiquitinases Gumby (OTULIN), OTUD7b, and TNFAIP3 (A20) in the OUT family were shown to negatively regulate NFkappaB activation through different mechanisms in different biological contexts [XREF_BIBR - XREF_BIBR]."
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"More detailed insights into the mechanisms that underlie NF-κB inactivation by A20 came from the discovery of an OTU domain at the N-terminus of A20 (Evans et al., xref )."
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"While TNFAIP3 is known to inhibit NF-kappaB activation and TNF-mediated apoptosis , PTGS2 is involved in the conversion of arachidonic acid to prostaglandin H2 [ 20 ] ."
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"The underlying mechanism for NF-kappaB inhibition by A20 is still unknown."
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"The conclusions from these in vivo studies are in line with results from an earlier in vitro study reporting a direct and noncatalytic mechanism of NF-κB inhibition by A20."
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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 "
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"NF-kappaB signaling is negatively regulated by deubiquitinases which include CYLD (cylindromatosis) and TNFAIP3 (also known as A20)."
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"Since the TNFAIP3 gene product, A20, functions to restrict NF-kappaB signaling, we focused on characterizing the binding of NF-kappaB subunits to the region."
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"TNFAIP3 can inactivate a number of NF-kappaB signaling molecules, like receptor interacting protein 1/2 (RIP1/2), TRAFF6, and IKKgamma (NEMO)."
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"Then A20 binds to NEMO / IKKgamma and suppresses NF-kappaB ."
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"In most cell types, A20 is inducible by proinflammatory cytokines or mitogens and inhibits NF-κB in a negative feedback loop."
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"It was proved that TNFAIP3, a key factor in NF-kappaB pathway, could attenuate NF-kappaB activation during the infection [XREF_BIBR] while nAChR, one of important ACh receptor, could also modulate the inflammatory responses through both NF-kappaB and JAK and STAT pathway [XREF_BIBR, XREF_BIBR]."
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"TNFAIP3 is known to reduce the inflammatory response by strongly inhibiting TNF-a/NF-kB signaling [29] ."
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"Our data suggest an additional mechanism for NF-κB inhibition by A20: In resting cells, a very low level of A20 expression prevents the basal processing of p105, p50 generation and the spontaneous act[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Once upregulated, TNFAIP3 inhibits NF-kappaB activity at multiple levels."
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"Some NF-kappaB pathway inhibitors are targeted by biallelic deletions (FAF1) [30] or inactivating alterations (deletion, mutation or hypermethylation) of TNFAIP3 (A20) [30,64]."
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"A20 inhibits NF-κB and multiple downstream immune and danger sensing receptors via multiple ubiquitin-editing and interacting domains ( xref – xref )."
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"TNFAIP3 is transcriptionally activated by NF-kappaB, allowing A20 to attenuate NF-kappaB signaling by deubiquitinating and hence inactivating TRAF6, MALT1, and IKKgamma, among other substrates."
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"TNIP1 interacts with A20 (TNFAIP3) to negatively regulate NF-kappaB."
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"TNFAIP3 can inactivate a number of NF-kappaB signalling molecules including receptor interacting protein-1/2 (RIP1/2), ubiquitin conjugating enzyme 13 (Ubc13) and IKKgamma (also known as NF-kappaB ess[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In the study " Breast Invasive Carcinoma " in The Cancer Genome Atlas, TNFAIP3 gene, which strongly inhibits NFkappaB signaling, and ESR1 gene encoding ER have significant tendency towards co-occurrence (P = 0.027, log odds ratio : 0.931) XREF_BIBR."
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"A20 inhibits NF-κB activation-induced by TNFα or by the overexpression of other proteins such as TRAF2 and receptor-interacting protein serine/threonine kinase 1 (RIPK1) proteins xref ."
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"It means that NFkappaB signaling is inhibited by TNFAIP3 expression in breast cancer patients expressing ESR1."
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"The biochemical mechanisms by which TNFAIP3 restricts NF-kappaB signaling are complex [ 4 ] ."
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"While the inhibition of NF-KB by TNFAIP3 can exacerbate hepatic I/R injury ( xref ), TNFAIP3 knockdown increases the infiltration of inflammatory cells into the liver ( xref )."
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"The role of CYLD in the inhibition of NF-κB has been reviewed elsewhere, xref and the main focus of this review article will be on A20 inhibition of NF-κB."
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"In this process, after activation of RXFP1 by rh-relaxin-2, an increase of TNFAIP3 mediated the reduction of NF-kappaB and functioned as a negative regulator of NF-kappaB."
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"Despite the important insight into A20 function from initial studies with A20-deficient mice, it was still yet to be elucidated how A20 inhibited NF-κB. A20 was subsequently found to contain an OTU DUB domain embedded in its N-terminus. xref , xref Overexpression of A20, but not a catalytically inactive DUB mutant, inhibited both RIP1 and TRAF6 ubiquitination. xref , xref A20 also contains seven C-terminal zinc finger domains, one of which functions as an E3 ligase."
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"The upstream inhibition of NF-κB by A20 impairs activation of the inhibitor of κB (IκB) kinase (IKK)."
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"Therefore, this model may be more relevant in T and B lymphocytes where the basal levels of A20 are high. xref Taken together, it has become increasingly clear that A20 may inhibit NF-κB independently of its deubiquitinase activity, although additional studies are clearly needed to further test and refine the different models of A20 inhibition of NF-κB."
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"However, the TNFAIP3 variants Ile310Thr and Gln709Arg suppressed the elevation of NF-kappaB reporter gene activity, similarly to the WT and Phe127Cys."
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"A20 reduces NFkappaB activation by inhibiting TNF receptor signaling and removing K63-linked ubiquitin chains conjugated to TRAF6 ( 45 , 46 ) ."
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"The inhibition of NF-κB by A20 may or may not be advantageous to the host defense mechanism against influenza virus infection."
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"TNFAIP3 encodes a ubiquitin-editing enzyme ( A20 ) which inhibits NF-kappaB activation and TNF-mediated apoptosis and acts as an anti-apoptotic protein in specific cell types [ 74 ] ."
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"Similarly , TNFAIP3 , which inhibits NF-kappaB activation , may have cell context dependent roles in colitis ."
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"A20 inhibits several key upstream signal transduction pathways of NF-kB induced by Toll-like receptor (TLR), the tumor necrosis factor receptor (TNFR), and retinoic acid-inducible gene I (RIG-I) in a feedback manner xref – xref by ubiquitination or deubiquitination of receptor interacting protein (RIP), TNFR-associated factor (TRAF) 6, and other molecules for either promoting target protein degradation or regulating interaction of the target proteins with other signaling molecules xref – xref ."
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"Indeed, CYLD is thought to primarily inhibit basal NF-κB activation, whereas in most cell types A20 inhibits activation-induced NF-κB. xref "
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"In addition to its well-ascribed functions as a DUB and ubiquitin-editing enzyme, there is also evidence that A20 may inhibit NF-κB via non-catalytic mechanisms. xref , xref For example, A20 disrupts the binding between E2 and E3 ubiquitin enzyme complexes to terminate IL-1R/TLR4 signaling. xref As mentioned earlier, a recent study suggests that A20 may also directly inhibit IKK through a noncatalytic mechanism dependent on ubiquitin binding via zinc finger domains. xref Therefore, what are the precise roles of the A20 OTU domain and the C-terminal zinc fingers in NF-κB and cell death inhibition?"
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"Indeed, we found that NF-kappaB activity was enhanced after radiation stimulation by the knockout of TNFAIP3."
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"The TNFAIP3 gene products function as anti-inflammatory molecules and negatively regulate the activity of NFkappaB."
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"In vitro studies suggest that A20 restricts NF-kappaB signals via C103-based DUB activity , while in vivo , DUB activity does not play a role in directly inhibiting NF-kappaB and is dispensable for the regulation of NF-kappaB signaling [ 15 ] ."
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"Since the ubiquitin enzyme A20 can inhibit NF-κB, IRG1 might be upregulated by A20 through its inhibition of NF-κB signaling."
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"It is therefore conceivable that the A20-dependent inhibition of NF-κB is due to the autophosphorylation of a recently identified serine cluster within the IKKs that down-regulates IKK activity upon p[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"TNFAIP3 inhibits NF-kappaB activation by exerting dual ubiquitin editing functions [XREF_BIBR]."
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"Based upon these findings, we hold the view that the inhibition of NF-κB by A20 should be an important protective mechanism of NPC senescence."
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"MALT1 paracaspase activity is constitutive in B-cell lymphomas, and inhibition of MALT1 catalytic activity preserves full-length A20, which then inhibits NF-κB and promotes toxicity towards B-cell lymphoma cells [ xref ]."
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"The loss-of-function mutation in TNFAIP3 diminishes the inhibitory effect of NF-kappaB, leads to increased inflammatory cytokine production and causes systemic inflammatory disease."
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"This suggests that A20-dependent NF-κB inhibition preventing the expression of pro-survival signals has a more important impact on cell fate then the antiapoptotic capacities of A20 in this cell type."
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"NF-kappaB regulates Tnfaip3 transcription and TNFAIP3 acts to negatively regulate NF-kappaB transactivation in islets."
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"The authors speculated that their results differed from those of Wertz et al. 45 due to their use of a different cell type implying that TNFAIP3 might inhibit NF-kappaB differently in different tissues."
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"Based upon these findings , we hold the view that the inhibition of NF-kappaB by A20 should be an important protective mechanism of NPC senescence ."
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"Meanwhile , A20 not only suppresses NF-kappaB activity , contributing to reduced production of TNF-alpha , IL-1beta , IL-6 , and other cytokines [ 19 , 44 ] , but also regulates IL-1beta and IL-17 through TRAF6 and MAPK [ 5 , 46 ] ."
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"A20 not only inhibits NF-kappaB signalling by modifying ubiquitylated protein substrates in multiple ways , but also blocks type I IFN signalling by removing K63-linked ubiquitin chains from TBK1 / IKKi , which is activated by the RIG-I / MDA5-mitochondrial antiviral signaling protein axis [ 21 ] ."
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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."
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"The biochemical mechanisms by which TNFAIP3 restricts NF-kappaB signaling are complex [XREF_BIBR]."
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"The increase of A20 blocks NF-kappaB in HMCs ."
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"XREF_BIBR, XREF_BIBR The model which then emerges is one in which TNFAIP3 is a pleiotropic inhibitor of NF-kappaB that can interact with numerous other proteins, enzymatically modulates ubiquitin chains, and oligomerizes into higher order structures."
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"TNFAIP3 protein as a zinc finger protein and ubiquitin shearing enzyme can suppress activated NF-kappaB signal pathway and induce apoptosis of TNF by activating ubiquitin ligase and ubiquitinase."
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"A20 can inhibit the E3 ligase activities of TRAF6 and inhibit NF-kappaB signaling [ 38 ] ."
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"Itch was further shown to regulate the targeting of A20 to substrates, and A20 was unable to inhibit NF-κB in the absence of Itch ( xref )."
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"A20 restricts NF-kappaB signaling downstream of TNFR1 , CD40 , TLRs , NOD-like receptors ( NLRs ) and IL-1R [ 164 ] [ 165 ] [ 166 ] [ 167 ] ."
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"Since it is known that induction of A20 reduces NF-kappaB activity and thus hBD2 levels , meningococcal-mediated A20 induction could be a way for the pathogen to dampen AMP expression ."
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"Conversely, others have reported that Cys103 and hence DUB activity is dispensable for A20 to inhibit NF-κB [ xref , xref ]."
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"The TNFAIP3 gene, encoded ubiquitin modifying enzyme known as A20, inhibits the activation of NF-kappaB signaling pathways, including these TNF and Toll like receptors XREF_BIBR."
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"A20 is phosphorylated by IKKβ on Ser381, leading to enhanced NF-κB inhibition by A20 [ xref ], although it is not clear if the DUB function of A20 is regulated by phosphorylation."
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"It is also evident that ZnF4 is not always required for A20 to inhibit NF-κB. For example, the inhibitory effect of overexpressed A20 on RIG-I- and virus-induced NF-κB and IRF3 activation was found to[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Deletion of the ubiquitin editing enzyme, TNFAIP3, contributes to lymphoid transformation, in part, by deregulating NFkappaB signaling."
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"Among them , TNFAIP3 suppresses nuclear factor-kappa B , and its germline mutations lead to HA202 , presenting with IBD and symptoms similar to those of Beh c et disease3 ."
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"For example, referring to NF-κB in Table 7 for the effect of zinc, ω-3 PUFAs and vitamin D on NF-κB: zinc has been shown to stimulate A20 which in turn inhibits NF-κB [ 366 ] or alternatively direct i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"YTHDF2 promotes temozolomide resistance in glioblastoma by activation of the Akt and NF-kappaB signalling pathways via inhibiting EPHB3 and TNFAIP3."
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"Mutation and deletion of A20 which inhibits NF-kB is found in leukemia [ xref , xref – xref ]."
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"It seems that A20 can inhibit NF-kB, possibly through inactivation of TRAF6 [81, 82]."
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"In this context, TNIP1, also known as ABIN (A20-binding inhibitor of NF-κB)-1, is a polyubiquitin-binding protein that interacts with TNFAIP3 to facilitate the binding of TNFAIP3 to polyubiquitinated mediators of NF-κB activation, and thus promotes the inhibition of NF-κB by TNFAIP3."
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"In this process , after activation of RXFP1 by rh-relaxin-2 , an increase of TNFAIP3 mediated the reduction of NF-kappaB and functioned as a negative regulator of NF-kappaB ."
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"However, A20 mutants lacking the N-terminal OTU domain remain capable of inhibiting NF-κB in overexpression studies xref ."
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"It is likely that CYLD and A20 inhibit NF-κB at different times during an inflammatory response."
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"High-penetrance heterozygous mutations in TNFAIP3 cause a haploinsufficiency of A20 (HA20), inadequate inhibition of NF-kappaB pathway, and an early onset autoinflammatory disorder."
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"TNFAIP3 can inhibit both NF-kappaB signaling and apoptosis, but the role of TNFAIP3 in vivo is likely cell and context dependent, owing to the ability of NF-kappaB to concomitantly induce transcription of inflammatory and anti-apoptotic genes."
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"Tnfaip3, which is also called A20, inhibits NF-kB signaling."
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"We find that both ABIN-1 and A20 inhibit NF-kappaB at the level of the IKK complex and that A20 inhibits activation of NF-kappaB by de-ubiquitination of NEMO/IKKgamma."
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"Loss of A20 expression may not be sufficient to activate NF-kappaB , because the NF-kappaB-mediated inflammatory disease that develops in A20 knockout mice requires MyD88-mediated activation of NF-kappaB , presumably in response to commensal gut flora ( 38 ) ."
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"Our previous study showed that the inactivation of NF-κB by A20, which results in a decrease in the inflammatory airway response, also follows this strategy [5] ."
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"Since TNIP1 is a negative regulator of the NF-κB pathway, so when the TNIP1-TNFAIP3 complex inhibits NF-κB, anti-apoptotic genes are not activated by NF-κB and hence apoptosis happens."
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"This enzyme removes Lys63-linked ubiquitin chains from RIP1 and adds Lys48 polyubiquitins to RIP1, thereby targeting this factor for proteasomal degradation, thus explaining the molecular mechanism of NF-κB inhibition by A20 ( xref )."
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"Here , we showed that lack of A20 in gingival keratinocytes significantly increased NF-kappaB activity and inflammatory cytokine and chemokine production in response to bacterial challenge ."
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"Among the genes suppressed> 3-fold by COUP-TFII were NFkappaB -responsive genes, i.e., CCL2, IL6, LTA, ICAM1, and TNFAIP3, as well as NFkappaB subunits (RELB), reflecting a possible role for COUP-TFII in downregulation of the NFkappaB pathway."
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"NF-kB responsive A20 and TNFAIP3 gene is known to down-regulate NF-kB signaling through the cooperative activity of its two ubiquitin editing domains XREF_BIBR."
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"TNFAIP3 inhibits NF-kappaB activation as well as TNFalpha-mediated apoptosis by binding to TRAF family adaptor proteins ( Heyninck et al ., 1999 ) ."
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"TNFAIP3 inhibits the activity of NF-kappaB, which strongly facilitates the tumor progression through MMP9 expression, and represses cell division and inflammation [XREF_BIBR - XREF_BIBR]."
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"A20 and TNFAIP3 inhibits NF-kappaB activation induced by the Kaposi 's sarcoma associated herpesvirus vFLIP oncoprotein."
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"Tumor necrosis factor-alpha (TNF-alpha) plays a critical role in TNFAIP3 suppressing the activity of NF-kappaB pathway [XREF_BIBR]."
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"This was based upon the published studies that A20, a zinc-finger ubiquitin-modifying enzyme, inhibits several upstream signaling pathways of NF-kB in a feedback manner by degradation or deactivation of signaling molecules via its dual functions of ubiquitination and deubiquitination xref , xref , xref ; A20-deficient Mфs display prolonged NF-κB activity xref , xref ; A20-silenced dendritic cells (DCs) express higher levels of costimulatory molecules and proinflammatory cytokines, and display a superior immunostimulatory ability xref ."
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"Inhibition of NF-κB by A20 has been ascribed to its sequential N-terminus mediated deubiquitination of signaling mediators such as RIP and NEMO, followed by C-terminus-mediated degradative polyubiquitination of the same substrates ( xref )."
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"A20 suppresses NF-kappaB signalling with inhibitory activity against key signalling molecular substrates , including TNF receptor-associated factor 6 ( TRAF6 ) 9 , receptor interacting protein 1 ( RIP1 ) 12,13 , and the IkappaB kinase complex ( IKK ) 14 ."
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"Taken together, the current study identifies a novel mechanism of inhibition of Brucella intracellular survival in macrophages, which involves suppression of activation of macrophages, inhibition of N[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Tumor necrosis factor alpha-induced protein 3 (TNFAIP3) negatively operates in a feedback loop to prevent NF-kB from being activated."
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"Therefore, we demonstrate that a pathological reduction in TNFAIP3 levels induced NF-kappaB and SMAD7 pathway activation, causing a deficiency in MSCs in ITP patients."
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"In another study, it was shown that miR-17-92 causes NF-kB signaling activation and the development of chronic myeloid leukemia by suppressing A20 (TNFAIP3)."
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"TNFAIP3 is induced by TNF and inhibits the NF-kappaB pathway by de-ubiquitination and ubiquitination of the TNF receptor interacting protein XREF_BIBR."
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"Additionally, Zn upregulates the expression of A20, which inhibits NF-κB and the subsequent production of cytokines ( xref )."
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"TNFAIP3 suppresses NF-kappaB activity through the removal of Lys-63-linked ubiquitin chains from , and / or adding degradation-inducing Lys-48 ubiquitin chains , to protein kinase RIPK1 upstream of IKK activation [ 39 ] ."
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"A20 also inhibits the activation of canonical NF-kB induced by TAK1 , thus A20 suppresses NF-kB activation by multiple mechanisms ."
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"For example, the expression of tumor necrosis factor-alpha inducing protein (TNFAIP3) that inhibits NF-kappaB activation and negatively regulates TNF-alpha signaling exhibited individual variability among our human donors."
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"Similar to OTUB1 , A20 suppresses NF-kappaB signaling by conjugating to E3 Ub-ligase [ 88 ] ."
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"Interestingly, A20-dependent inhibition of NF-κB has been shown to promote necrotic cell death, a function that contrasts with its antiapoptotic role in cytokine-induced apoptosis [ xref ]."
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"Intriguingly, the silencing of TNFAIP3 by its siRNA in healthy SGEC increased NF-kappaB activation that could explain the deregulated cytokines production observed in SS."
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"TNFAIP3 can interact with TRAF1/TRAF2 and inhibit the activation of the NF-kappa-B pathway [46, 47]."
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"A20 restricts NF-kappaB signaling downstream of TNFR1 , CD40 , TLRs , NOD-like receptors ( NLRs ) and IL-1R [ 164 ] , [ 165 ] , [ 166 ] , [ 167 ] ."
| PMC