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TNFAIP3 activates NFkappaB. 53 / 55
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"Accordingly, overexpression of a miR-29b-refractory isoform of TNFAIP3 restored NF-kappaB and extrinsic apoptosis, confirming that TNFAIP3 is a functionally relevant target of miR-29b."
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"Consistent with our findings in the gut derived lethal infection model, i.p. injection of the PC resulted in downregulation of IRF3 and the upregulation of NF-kB Inhibitor Alpha (NFKBIA), NF-kB Inhibitor Beta (NFKBIB), and TNF Alpha Induced Protein 3 (TNFAIP3), known NF-kappaB pathway inhibitors XREF_BIBR, XREF_BIBR, in the cecum, liver, and spleen, 20h post PC injection in AC-FMT mice."
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"Up-regulation of the inhibitor of NF-kappaB activation TNFAIP3, also known as A20, in the DM samples, along with its binding partner, TNFAIP3 interacting protein 1 (TNIP1), and RELA suggests a potenti[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Accordingly, overexpression of an miR-29b-refractory isoform of TNFAIP3 restored NF-kappaB and extrinsic apoptosis, confirming that TNFAIP3 is a functionally relevant target of miR-29b."
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"Conclusion : Down-regulated MiR-128-3p significantly suppressed the inflammation response of RA through suppressing the activity of NF-kappaB pathway, which was mediated by TNFAIP3."
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"Tnfaip3 OTU and OTU and Tnfaip3 ZF4 and ZF4 cells produced less of the NF-kappaB dependent mRNAs IL-6 and cellular inhibitor of apoptosis protein 2 (cIAP2), and exhibited less NF-kappaB signaling than Tnfaip3 -/- cells, suggesting that neither A20 's C103 motif nor its ZF4 motif are singly responsible for all of A20 's functions during TNF signaling (XREF_SUPPLEMENTARY)."
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"Ji et al. have shown in a colorectal cancer model that the primary tumor released integrin beta like 1 rich extracellular vesicles to lungs and liver, which converted resident fibroblasts to cancer associated fibroblast (CAF) in the lungs and activated hepatic stellate cells in the liver by stimulating TNFAIP3 mediated NF-kappaB signaling pathway [XREF_BIBR]."
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"Our list also contained well established NF-kappaB targets such as MYC, TNFAIP3, and NFKBIA, attesting to the validity of our analyses."
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"Synergistic activation of NF-kappaB by TNFAIP3 (A20) reduction and UBE2L3 (UBCH7) augment that synergistically elevate lupus risk."
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"Michael et al. and Ye et al. identified that miR-19b positively regulates NF-kappaB signaling by targeting the inhibitory regulators of NF-kappaB signaling including A20 and Tnfaip3, Rnf11, Fbxl11 and[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"This signature of EGFR TKI induced NF-kappaB output consisted of 36 NF-kappaB target genes, including established regulators of NF-kappaB signaling and cell survival such as TNFAIP3, BIRC3, and IL6 (XREF_FIG and XREF_SUPPLEMENTARY)."
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"This effect may be mediated by changes in NF-kappaB activity caused by variable expression of TNFAIP3."
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"Transfection of mutant truncated A20 and TNFAIP3 prolonged NF-kappaB activation due to reduced deubiquitinating function."
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"In summary, the present study explored the potential mechanism of MiR-128-3p in RA, with the results of MiR-128-3p were significantly increased, the T cells and the NF-kappaB signaling pathway were activated, while down-regulating the expression of MiR-128-3p significantly suppressed the activation of T cells and the NF-kappaB signaling pathway, which was mediated by TNFAIP3, and further relieved the symptom of RA."
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"* Haploinsufficiency of TNFAIP3 (A20) activates the NF-kappaB pathway, leading to cellular proliferation."
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"Western blotting indicated that A20 overexpression significantly reduced total levels of UBC13, phosphorylated IκBα S32, p65, and phosphorylated p65 S536, indicating effective suppression of the NF-κB activation by A20 in cultured neurons ( xref , xref )."
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"In conclusion, these results indicate that ectopic TNFAIP3 or NKIRAS2 can restore miR-125b-induced activation of NF-kappaB."
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"We next used a luciferase reporter assay to further confirm the modulation of NF-κB activation by A20 in neurons."
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"In our previously reported study, we also showed that TALEN mediated TT> A enhancer knockout leads to reduced expression levels of TNFAIP3 and significant increases in NF-kappaB signaling activity."
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"In another study on HCV-infected patients, a genetic variant of TNFAIP3 was shown to be present only in tumors of HCV-infected NHL patients. xref Consistent with the high expression of NF-κB and proliferation signaling in HBsAg + FLs, it is possible that NF-κB signaling activated by TNFAIP3 mutations may provide a survival or proliferation signal to tumor cells in HBV-infected FLs."
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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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"Mechanistically, the primary CRC-derived ITGBL1-enriched EVs stimulate the TNFAIP3-mediated NF-kappaB signaling pathway to activate fibroblasts."
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"NF-kappaB activation in ABC DLBCL can also be augmented by inactivation of TNFAIP3, which encodes A20, a negative regulator of IKK [XREF_BIBR]."
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"In arthritis subjects, decreased basal levels of TNFAIP3 results in greater fold induction of NF-kappaB upon stimulation."
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"Importantly, direct transcriptional NF-kappaB targets, such as TNF alpha induced protein 3 (TNFAIP3, synonym : A20) or nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IkappaBalpha) are essential for the fast and efficient shut-down of this pathway in terms of a negative feedback regulation."
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"As such, CO suppression of miR-155 and TNFAIP3 could be proinflammatory and allow early phase inhibition of NF-kappaB signaling by CO to recover."
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"miR-155 also regulates PU1 and CD10 modulating activated B-cell formation through NF-kB [XREF_BIBR], and miR-125a/b can regulate TNFAIP3 promoting activation of NF-kB [XREF_BIBR]."
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"The C-terminal region (containing the functional zinc finger structures) mediates A20 dimerization and binding to several other proteins that might be involved in the inhibition of NF-kB activation and apoptosis by A20 [ xref ]."
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"For example, TNFAIP3 is a transcriptional target of NF-kappaB, serves as a " global " feedback regulator to attenuate NF-kappaB activity by inactivation of NEMO, TRAF6, and RIP1, thus negatively regul[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Mutations of CARD11 but not TNFAIP3 may activate the NF-kappaB pathway in primary CNS lymphoma."
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"By targeting TNFAIP3, miR-125a/b directly inhibits the expression level of TNFAIP3, and induces NF-kappaB activity, which leads to increased aggressiveness in both cell line assays and in primary tumors [XREF_BIBR]."
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"Multiple downstream components of TNF signaling have been associated in autoimmunity, most notably the tumor necrosis factor inducible protein A20 (TNFAIP3), which terminates TNF- and pattern recognition receptor induced responses of the transcription factor NF-kappaB."
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"This dual function is clearly maintained in islets, suggesting that inhibition of NF-κB activation by A20 is an important component of the natural physiological role of A20."
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"IkappaBalpha and TNFAIP3 are the transcriptional targets of NF-kappaB, and their expression following NF-kappaB activation could serve as an auto-negative feedback."
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"Thus, TNFAIP3 inactivation can potentially augment NF-kappaB activation triggered by signalling from multiple surface receptors.This occurs in ~ 5% of occular adnexal MALT lymphoma, and comprises nove[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Many up-regulated genes are known NF-kappaB targets, including Tnfaip3, Birc3, Nfkbia, Ccl20, Ccl2, Cxcl10, Icam1, Tnf, RelB, Csf1 and Bcl3."
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"However breakdown of TLR tolerance is fortified by more checkpoint mechanisms : MYD88 L265P -induced proliferation was rapidly curtailed by Tnfaip3 mediated shutdown of NF-kappaB and by Bcl2 inhibited, Bim dependent apoptosis."
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"Due to the inhibitory effect of A20 on the NFkappaB signaling pathway, TNFAIP3 polymorphisms also cause hyperactive NFkappaB signaling."
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"A20 (TNFAIP3), TNF alpha inducible protein 3; IkappaBalpha, inhibitor of kappaB alpha subunit; IKK, IkappaB kinase; IKKK, IKK kinase; IRAK1 interleukin-1 receptor associated kinase 1; MEKK3, mitogen activated protein kinase kinase kinase 3; NF-kappaB, nuclear factor-kappaB; RIP, receptor interacting protein; TAK1, transforming growth factor-beta-activated kinase 1; TNFalpha, tumor necrosis factor alpha; TNFR, TNF receptor; TRAF2, tumor necrosis factor receptor associated factor 2."
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"A20 and AKT also activate NF-κB, which then reduces the activity of A20 in a negative feedback loop."
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"Five of the immune related genes are involved in NF-kappaB signaling including two kinases, Bone Morphogenetic Protein Receptor Type 1A (BMPR1A) and Protein Kinase C Zeta (PRKCZ), two enzymes, TNF Alpha Induced Protein 3 (TNFAIP3) and Ubiquitin Conjugating Enzyme E2 N (UBE2N), and one transmembrane receptor, Insulin Like Growth Factor 1 Receptor (IGF1R)."
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"In view of the indicated requirement of the NEMO-RIP interaction for activation of the signalosome, it was of interest to determine whether the inhibition of NF-κB activation by A20 reflects inhibitio[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"The CBM complex promotes lymphocyte proliferation and survival by cleaving the NF-κB inhibitors RelB, A20, and BCL-10, which activates NF-κB [ xref ]."
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"Recently, somatic mutation of A20 gene which constitutively activate NF-κB had been reported by several investigators [ xref – xref ]."
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"TNFAIP3 inactivation by any mechanism contributes to lymphoma pathogenesis by promoting unchecked NFkappaB signaling and enhanced-cell survival [XREF_BIBR]."
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"The underlying mechanism of negative feedback regulation of NF-κB activation by A20 is still unclear."
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"Second, the inhibitory mechanism acting on NF-κB activation by I-TRAF, A20, and TRIP appears to be different."
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"It is known that the constitutive NF-kappaB activation in ABC-DLBCL is caused by individual or overlapping known mutations like MYD88 L265P, CARD11, TNFAIP3 and CD79B/A [XREF_BIBR], which are involved in antigen specific B-cell receptor (BCR) and Toll like receptor (TLR) induced NF-kappaB activation."
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"Coexpression of A1 rescues A20 expressing RPTECs from TNF-mediated apoptosis despite inhibition of NF-κB activation by A20."
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"Blocking NF-κB activation by A20 also takes place in a TNF-α-dependent manner."
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"Many of these genes have known roles in immunity and include Tnf, Il12b, and Cd40, as well as genes that regulate canonical NF-kappab signaling, such as Tnfaip3 (which encodes A20), Nfkbiz, and Nfkbia (XREF_FIG, left)."
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"Inhibition of NF-κB Activation by A20 Is Stimulus-dependent."
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"TNFAIP3, a negative regulator of inflammation that inhibits NF-kB (nuclear factor kappa-B) and TNF (tumor necrosis factor)-mediated pathways, has been linked to several immune mediated diseases like T1D, systemic lupus erythematosus, and rheumatoid arthritis [XREF_BIBR, XREF_BIBR]."
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