IndraLab
Statements
reach
"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."
reach
"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)."
reach
"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]."
sparser
"Considering these complex interactions between A20 and NF-kB, the involvement of A20 and NF-kB in HBV infection and the liver tissue homeostasis and the pathogenesis of liver diseases, and the role of A20 in the regulation of innate anti-viral immune response, the comprehensive link between TNFAIP3 polymorphisms and chronic HBV infection and HBV-related diseases may be complex and needs in-depth studies."
sparser
"Moreover, a previous study demonstrated that the SFTSV NSs binds and inhibits A20-binding inhibitor of NF-κB 2 (ABIN2) to form complex with its interaction partners, tumor progression locus 2 (TPL2) and p105, resulted in the marked upregulation of anti-inflammatory cytokine IL-10 ( xref ) [ xref ]; p105/TPL2 complex regulates the expression of inflammatory genes, including anti-inflammatory gene IL10 , in which the signaling cascade is inhibited by ABIN2 binding to this complex."
TNFAIP3 is modified
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TNFAIP3 is phosphorylated.
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sparser
"In consideration of the time to effect 50% apoptosis, A20.2J lymphoma cells can resist the effects of Man-A as much as 8 times longer than their WEHI-231 counterparts (above and ref. xref ) and PP1α remains stably phosphorylated in Man-A resistant A20.2J and prostate cancer cells ( xref )."
TNFAIP3 is ubiquitinated.
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sparser
"As TCR stimulation induced a modification of the
molecular weight of A20-bound to RNF114, suggesting a post-translational
modification of A20 ( xref ), we checked
whether RNF114-induced A20 ubiquitylation was increased after phorbol
12-myristate 13-acetate (PMA)/ionomycin in HEK293 cells."
sparser
"Earlier studies on A20 in inflammatory and autoimmune diseases showed that A20 is associated with a complex regulator of ubiquitylation of canonical NF-κB and cell-survival signals A20: linking a complex regulator of ubiquitylation to immunity and human disease [ xref – xref , xref , xref ]."
sparser
"Whilst the UBAN domain of NEMO is required for TNF-α (tumor necrosis factor)-induced NF-kB activation [ xref ], the same domain in ABIN-1 binds to linearly ubiquitinated NEMO and A20 ubiquitin-editing enzyme and promotes deubiquitination and termination of NF-κB signaling [ xref ]."
TNFAIP3 is methylated.
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TNFAIP3 is glycosylated.
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2
sparser
"It also maps a novel molecular link between decreased A20 levels, such as in subjects harboring specific TNFAIP3 single nucleotide polymorphisms or in poorly controlled diabetics where O-glycosylation of the A20 protein leads to its degradation and increased incidence of EC dysfunction and atherogenesis ( xref , xref )."
sparser
"Strikingly, Gerber’s lab has recently shown that the transcriptional cooperation between GR and NF-κB constitutes the main mechanism explaining the augmentation of TNF-induced A20 expression by dexamethasone (i.e., TNFAIP3, TNF alpha induced protein 3) in airway epithelial and smooth muscle cells ( xref ; xref )."
reach
"Thirty‐eight genes involved in the defense response to virus, including bone marrow stromal antigen (BST2)/tetherin and MX Dynamin Like GTPase 2/myxovirus resistance protein 2 (MX2) and tumor necrosis factor‐alpha‐induced protein 3 (TNFAIP3) were overexpressed in VKC (Table 1 and Figure 1)."
sparser
"Other loci and genes involved in inflammatory pathways that have been implicated in RA with a modest effect size include CTLA4 (negative regulator of T cell activation) ( xref ), STAT4 (transcription factor involved in intracellular cytokine signaling) ( xref ), TNFAIP3 [inhibitor of nuclear factor κ-light chain enhancer of activated B cells (NF-κB) signaling; it is required for termination of tumor necrosis factor (TNF)-induced signals] ( xref ), TRAF1-C5 (locus including TRAF1 , which encodes a negative regulator of intracellular TNF signaling that binds to TNFAIP3, and C5 , which encodes complement factor C5) ( xref ), IL2/21 [encoding interleukin (IL)-2 and IL-21] ( xref ), CD40 (surface receptor present in various immune cells, including B cells, where it is crucial for B-T cell interaction) ( xref ), IL2RA/IL2RB (encoding IL-2 receptor alpha and beta chains, respectively), ( xref , xref ) IL6R [encoding the IL-6 receptor (IL-6R)] ( xref ) or CCL21 (lymphocyte chemokine) ( xref ), among many others ( xref , xref , xref )."
TNFAIP3 affects activation
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92
sparser
"A20-TRAF6 interactions were increased in LPS-stimulated bid- deficient glia upon TRAF6-FLAG overexpression (Fig. xref ), with a similar pattern observed in ubiquitin-HA (Ub-HA) overexpressing bid- deficient glia at rest and upon LPS activation (Additional file xref : Figure S1A)."
sparser
"Multiple subdomains of A20 contribute to its inhibitory capacity ( xref and xref ) ( xref ), the best characterized of which is the N-terminal OTU (ovarian tumor) domain, which encodes DUB activity and is proposed to be important for the association of A20 with TRAF6 ( xref , xref )."
sparser
"Upon recruitment of A20 to TRAF6, the E2 enzymes are displaced from TRAF6 leading to an attenuation of TRAF6 E3 ligase activity. xref At later times after LPS stimulation, Ubc13 and UbcH5c are ubiquitinated and degraded by the proteasome in an A20 and TAX1BP1-dependent manner. xref TAX1BP1 is also essential for A20 to initially interact with TRAF6. xref Notably, TRAF6 is not degraded by LPS stimulation suggesting that the ubiquitin-editing function of A20 may be specific for RIP1."
sparser
"Moreover, we previously demonstrated that Bid associates with TRAF6 in both unstimulated and LPS-stimulated conditions [ xref ], and this study strengthens our previous finding by demonstrating A20-TRAF6 interactions are increased in both basal and LPS-activated bid -deficient glia."
sparser
"A previous study reported that A20 plays a role in deubiquitination to cleave the K63‐linkage ubiquitination of TRAF6 or directly affect the K63‐linkage ubiquitination of Beclin1 to inhibit autophagy in macrophages. xref In addition, the inhibition of TRAF6 ubiquitin‐ligase activity with PRDX1 led to the downregulation of autophagy activation. xref It has been shown that LPS‐induced A20 expression facilitates TRAF6 degradation in human peripheral blood mononuclear cells. xref These studies indicate A20‐TRAF6 axis is closely related to autophagy."
sparser
"Nonetheless, depletion of TRIP6 can significantly enhance the association of A20 or CYLD with TRAF6 in ovarian cancer cells and promote the binding of A20 to TRAF6 in glioblastoma cells, suggesting that targeting TRIP6 may prove to be an effective strategy to restore the function of A20 and CYLD in restricting the NF-κB activity in these cancer cells."
sparser
"Nonetheless, depletion of TRIP6 by either shRNA ( xref ) or Cas9/sgRNA ( xref ) not only enhanced the association of TRAF6 with A20, but also with CYLD in untreated and treated cells, suggesting a significant role for TRIP6 in antagonizing the binding of TRAF6 to both A20 and CYLD in ovarian cancer cells."
sparser
"In this regard, here we provide evidence that the adaptor protein TRIP6 (thyroid hormone receptor-interacting protein 6), a specific interacting protein of the LPA2 receptor but not other LPA receptors, recruits TRAF6 to the LPA2 receptor and enhances the E3 ligase activity of TRAF6 by antagonizing the association of A20 and CYLD to TRAF6."
sparser
"Wild-type mouse embryonic fibroblasts (MEFs) or MEFs that lack expression of A20 ( A20 −/− ) or TAX1BP1 ( Tax1bp1 −/− ) were treated with IL-1 for various times, and the interactions between TRAF6, A20, and TAX1BP1 were monitored by immunoprecipitations and protein immunoblotting ( xref and xref )."
eidos
"The K63-linkage ubiquitination facilitates TRAF6 to exert ubiquitin function , while the K48-linkage ubiquitination is involved in the degradation of TRAF6.22 Therefore , this result indicates that A20 could inhibit ubiquitination of TRAF6 , and accelerate TRAF6 degradation to suppress autophagy in hPDLCs under hypoxia ."
sparser
"Whilst the UBAN domain of NEMO is required for TNF-α (tumor necrosis factor)-induced NF-kB activation [ xref ], the same domain in ABIN-1 binds to linearly ubiquitinated NEMO and A20 ubiquitin-editing enzyme and promotes deubiquitination and termination of NF-κB signaling [ xref ]."
sparser
"Coronaviruses (CoVs) are a large family of RNA viruses that cause respiratory tract infections, ranging from the mild common cold to serious diseases such as severe acute respiratory syndrome (SARS), middle east www.advancedsciencenews.com www.advancedscience.com
Inhibiting TLR/NF-B signaling [ 100] TRIF USP19 K27 Inhibiting TLR3/4-mediated signaling [98] TRAF6 A20 K63 Terminating TLR-induced activity [91] USP4 K63 Preventing NF-B and AP1 activation, inhibiting TLR/IL-1R signaling [ 102] USP 10 K63 Interacting with TANK and MCPIP1, terminating NF-B activation in response to TLR [ 104] MYSM1 K63 Terminating TLR-mediated antiviral responses [ 101] OTUD1 K48 Inhibiting IFN production [ 175] OTUB1/2 K63 Inhibiting antiviral responses [ 172] TRAF3 MYSM1 K63
Terminating TLR-mediated antiviral responses [ 101] UCHL1 K63 Inhibiting IFN production [ 103] OTUD1 K48 Inhibiting IFN production [ 175] OTUB1/2 K63 Inhibiting antiviral responses [ 172] RIP1 (also known as RIPK1) A20 K63
Inhibiting NF-B signaling [92] CYLD K63 Inhibiting NF-B signaling [95] A20 K48 Inducing A20 degradation with E3 ligase activity, inhibiting NF-B signaling [92] NEMO A20 N/A Binding to ubiquitinated NEMO, blocking IKK phosphorylation, inhibiting NF-B activation [93] CYLD M1 Inhibiting NF-B signaling [97] USP10 M1 Interacting with NEMO via MCPIP1, inhibiting the genotoxic NF-B signaling [40] TAK1 USP18 K63 Inhibiting TLR/NF-B signaling [ 116] RIG-I USP5 K48
Interacting with STUB1, mediating RIG-I degradation, enhancing VSV replication [ 174] CYLD K63 Inhibiting IFN production [ 162] USP3 K63 Inhibiting antiviral responses upon viral infection [ 164] USP21 K63 Inhibiting antiviral responses [ 165] USP14 K63 Inhibiting antiviral responses [ 167] USP27X K63 Inhibiting antiviral responses [ 168] USP15 K63 Inhibiting antiviral responses [ 169] MAVS YOD1 K63 Inhibiting IRF3 and p65 activation, IFN-production, inhibiting antiviral responses [ 170] OTUD1 K48 Inhibiting IFN production [ 175] OTUD3 K63 Inhibiting antiviral responses [ 171] STING USP49 K63 Inhibiting antiviral responses after HSV-1 infection [ 217] USP21 K63 Inhibiting type I interferon production induced by DNA virus [ 219] USP13 K27/33 Impairing the recruitment of TBK1 to STING, inhibiting antiviral responses [ 218] USP21 K27 Inhibiting type I interferon production induced by DNA virus [ 219] USP22 K27 Interacting with USP13 [ 174] TBK1 A20 K63 Inhibiting antiviral responses with TAX1BP1 [ 232] USP2b K63 inhibiting TBK1 kinase activity, terminating TBK1 activation, inhibiting IFN-signaling [ 233] USP7 K48 Interacting with and stabilizing TRIM27, inhibiting antiviral type I IFN signaling [ 235] USP38 K33 Interacting with TBK1 via NLRP4, allowing DTX4-and TRIP-mediated K48-linked polyubiquitination, promoting TBK1 degradation, inhibiting IFN-I signaling [ 236] IRF3 OTUD1 K63 Inhibiting IRF3 nuclear translocation and its transcriptional activity [ 244] K6 Disassociation of IRF3 from the promoter region of target genes, inhibiting type I IFN induction [ 245] Signaling activation TRAF3 USP25 K48 Preventing TRAF3 degradation following virus infection, facilitating antiviral responses [ 117, 180] OTUD7B K48 Inhibiting TRAF3 proteolysis, preventing aberrant non-canonical NF-B activation [ 118] RIG-I USP15 K63
Removing K48-linked polyubiquitin chains on TRIM25, promoting IFN-I expression [ 181] USP4 K48 Stabilizing RIG-I, prolonging IFN induction [ 177] USP17 K48 Stabilizing RIG-I, facilitating antiviral responses [ 176] (Continued)
Adv."
sparser
"A20 inhibition of IKK was dependent on A20 binding to NEMO which was induced by K63-linked polyubiquitin chains. xref The binding of A20 with NEMO occurred rapidly upon IL-1 stimulation (2–5 min) in HeLa cells. xref Therefore, the polyubiquitin chains that serve to activate IKK also serve a dual function in its negative regulation by the recruitment of A20 to NEMO."
sparser
"Enforced expression of NEMO in cells revealed that NEMO can both promote and block NF-kappaB activation and dramatically augments the phosphorylation of c-Jun. The findings suggest that the signaling activities of the IKK signalosome are regulated through binding of NEMO to RIP and A20 within the p55 TNF receptor complex."
sparser
"Considering these complex interactions between A20 and NF-kB, the involvement of A20 and NF-kB in HBV infection and the liver tissue homeostasis and the pathogenesis of liver diseases, and the role of A20 in the regulation of innate anti-viral immune response, the comprehensive link between TNFAIP3 polymorphisms and chronic HBV infection and HBV-related diseases may be complex and needs in-depth studies."
sparser
"Moreover, a previous study demonstrated that the SFTSV NSs binds and inhibits A20-binding inhibitor of NF-κB 2 (ABIN2) to form complex with its interaction partners, tumor progression locus 2 (TPL2) and p105, resulted in the marked upregulation of anti-inflammatory cytokine IL-10 ( xref ) [ xref ]; p105/TPL2 complex regulates the expression of inflammatory genes, including anti-inflammatory gene IL10 , in which the signaling cascade is inhibited by ABIN2 binding to this complex."
reach
"As A20 ZF4 proteins are recruited poorly to TNFR signaling complexes, the presence of normal NF-kappaB signaling in Tnfaip3 OTU and ZF4 cells also raises the interesting possibility that A20 OTU proteins may dimerize with A20 ZF4 proteins and recruit the latter to TNFR signaling complexes in Tnfaip3 OTU and ZF4 cells."
eidos
"Seeking a possible link between reduced NF-kappaB activation by the E protein and increased inflammasome activation and TNFalpha release , we found that expression of Tnfaip3 ( A20 ) , which is activated by NF-kappaB and mediates important negative feedback on expression of inflammatory genes , was reduced by the E protein in LPS + poly ( I :C ) treated cells ( Supplementary Fig. S4B ) ."
sparser
"Whilst the UBAN domain of NEMO is required for TNF-α (tumor necrosis factor)-induced NF-kB activation [ xref ], the same domain in ABIN-1 binds to linearly ubiquitinated NEMO and A20 ubiquitin-editing enzyme and promotes deubiquitination and termination of NF-κB signaling [ xref ]."
sparser
"Coronaviruses (CoVs) are a large family of RNA viruses that cause respiratory tract infections, ranging from the mild common cold to serious diseases such as severe acute respiratory syndrome (SARS), middle east www.advancedsciencenews.com www.advancedscience.com
Inhibiting TLR/NF-B signaling [ 100] TRIF USP19 K27 Inhibiting TLR3/4-mediated signaling [98] TRAF6 A20 K63 Terminating TLR-induced activity [91] USP4 K63 Preventing NF-B and AP1 activation, inhibiting TLR/IL-1R signaling [ 102] USP 10 K63 Interacting with TANK and MCPIP1, terminating NF-B activation in response to TLR [ 104] MYSM1 K63 Terminating TLR-mediated antiviral responses [ 101] OTUD1 K48 Inhibiting IFN production [ 175] OTUB1/2 K63 Inhibiting antiviral responses [ 172] TRAF3 MYSM1 K63
Terminating TLR-mediated antiviral responses [ 101] UCHL1 K63 Inhibiting IFN production [ 103] OTUD1 K48 Inhibiting IFN production [ 175] OTUB1/2 K63 Inhibiting antiviral responses [ 172] RIP1 (also known as RIPK1) A20 K63
Inhibiting NF-B signaling [92] CYLD K63 Inhibiting NF-B signaling [95] A20 K48 Inducing A20 degradation with E3 ligase activity, inhibiting NF-B signaling [92] NEMO A20 N/A Binding to ubiquitinated NEMO, blocking IKK phosphorylation, inhibiting NF-B activation [93] CYLD M1 Inhibiting NF-B signaling [97] USP10 M1 Interacting with NEMO via MCPIP1, inhibiting the genotoxic NF-B signaling [40] TAK1 USP18 K63 Inhibiting TLR/NF-B signaling [ 116] RIG-I USP5 K48
Interacting with STUB1, mediating RIG-I degradation, enhancing VSV replication [ 174] CYLD K63 Inhibiting IFN production [ 162] USP3 K63 Inhibiting antiviral responses upon viral infection [ 164] USP21 K63 Inhibiting antiviral responses [ 165] USP14 K63 Inhibiting antiviral responses [ 167] USP27X K63 Inhibiting antiviral responses [ 168] USP15 K63 Inhibiting antiviral responses [ 169] MAVS YOD1 K63 Inhibiting IRF3 and p65 activation, IFN-production, inhibiting antiviral responses [ 170] OTUD1 K48 Inhibiting IFN production [ 175] OTUD3 K63 Inhibiting antiviral responses [ 171] STING USP49 K63 Inhibiting antiviral responses after HSV-1 infection [ 217] USP21 K63 Inhibiting type I interferon production induced by DNA virus [ 219] USP13 K27/33 Impairing the recruitment of TBK1 to STING, inhibiting antiviral responses [ 218] USP21 K27 Inhibiting type I interferon production induced by DNA virus [ 219] USP22 K27 Interacting with USP13 [ 174] TBK1 A20 K63 Inhibiting antiviral responses with TAX1BP1 [ 232] USP2b K63 inhibiting TBK1 kinase activity, terminating TBK1 activation, inhibiting IFN-signaling [ 233] USP7 K48 Interacting with and stabilizing TRIM27, inhibiting antiviral type I IFN signaling [ 235] USP38 K33 Interacting with TBK1 via NLRP4, allowing DTX4-and TRIP-mediated K48-linked polyubiquitination, promoting TBK1 degradation, inhibiting IFN-I signaling [ 236] IRF3 OTUD1 K63 Inhibiting IRF3 nuclear translocation and its transcriptional activity [ 244] K6 Disassociation of IRF3 from the promoter region of target genes, inhibiting type I IFN induction [ 245] Signaling activation TRAF3 USP25 K48 Preventing TRAF3 degradation following virus infection, facilitating antiviral responses [ 117, 180] OTUD7B K48 Inhibiting TRAF3 proteolysis, preventing aberrant non-canonical NF-B activation [ 118] RIG-I USP15 K63
Removing K48-linked polyubiquitin chains on TRIM25, promoting IFN-I expression [ 181] USP4 K48 Stabilizing RIG-I, prolonging IFN induction [ 177] USP17 K48 Stabilizing RIG-I, facilitating antiviral responses [ 176] (Continued)
Adv."
sparser
"A20 inhibition of IKK was dependent on A20 binding to NEMO which was induced by K63-linked polyubiquitin chains. xref The binding of A20 with NEMO occurred rapidly upon IL-1 stimulation (2–5 min) in HeLa cells. xref Therefore, the polyubiquitin chains that serve to activate IKK also serve a dual function in its negative regulation by the recruitment of A20 to NEMO."
sparser
"Enforced expression of NEMO in cells revealed that NEMO can both promote and block NF-kappaB activation and dramatically augments the phosphorylation of c-Jun. The findings suggest that the signaling activities of the IKK signalosome are regulated through binding of NEMO to RIP and A20 within the p55 TNF receptor complex."
sparser
"Enforced expression of NEMO in cells revealed that NEMO can both promote and block NF-kappaB activation and dramatically augments the phosphorylation of c-Jun. The findings suggest that the signaling activities of the IKK signalosome are regulated through binding of NEMO to RIP and A20 within the p55 TNF receptor complex."
"The amino-terminal domain of A20, which is a de-ubiquitinating (DUB) enzyme of the OTU (ovarian tumour) family, removes lysine-63 (K63)-linked ubiquitin chains from receptor interacting protein (RIP), an essential mediator of the proximal TNF receptor 1 (TNFR1) signalling complex"
"A20 contains deubiquitinase and E3 ligase domains and thus has been proposed to function as a ubiquitin-editing enzyme downstream of TNFR1 by inactivating ubiquitinated RIP1"
"While the N-terminal domain of A20 is a deubiquitinating enzyme (DUB) for Lys63-linked polyubiquitinated signaling mediators such as TRAF6 and RIP, its C-terminal domain is a ubiquitin ligase (E3) for Lys48-linked degradative polyubiquitination of the same substrates"
reach
"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."
sparser
"A20-TRAF6 interactions were increased in LPS-stimulated bid- deficient glia upon TRAF6-FLAG overexpression (Fig. xref ), with a similar pattern observed in ubiquitin-HA (Ub-HA) overexpressing bid- deficient glia at rest and upon LPS activation (Additional file xref : Figure S1A)."
sparser
"Multiple subdomains of A20 contribute to its inhibitory capacity ( xref and xref ) ( xref ), the best characterized of which is the N-terminal OTU (ovarian tumor) domain, which encodes DUB activity and is proposed to be important for the association of A20 with TRAF6 ( xref , xref )."
sparser
"Upon recruitment of A20 to TRAF6, the E2 enzymes are displaced from TRAF6 leading to an attenuation of TRAF6 E3 ligase activity. xref At later times after LPS stimulation, Ubc13 and UbcH5c are ubiquitinated and degraded by the proteasome in an A20 and TAX1BP1-dependent manner. xref TAX1BP1 is also essential for A20 to initially interact with TRAF6. xref Notably, TRAF6 is not degraded by LPS stimulation suggesting that the ubiquitin-editing function of A20 may be specific for RIP1."
sparser
"Moreover, we previously demonstrated that Bid associates with TRAF6 in both unstimulated and LPS-stimulated conditions [ xref ], and this study strengthens our previous finding by demonstrating A20-TRAF6 interactions are increased in both basal and LPS-activated bid -deficient glia."
sparser
"A previous study reported that A20 plays a role in deubiquitination to cleave the K63‐linkage ubiquitination of TRAF6 or directly affect the K63‐linkage ubiquitination of Beclin1 to inhibit autophagy in macrophages. xref In addition, the inhibition of TRAF6 ubiquitin‐ligase activity with PRDX1 led to the downregulation of autophagy activation. xref It has been shown that LPS‐induced A20 expression facilitates TRAF6 degradation in human peripheral blood mononuclear cells. xref These studies indicate A20‐TRAF6 axis is closely related to autophagy."
sparser
"Nonetheless, depletion of TRIP6 can significantly enhance the association of A20 or CYLD with TRAF6 in ovarian cancer cells and promote the binding of A20 to TRAF6 in glioblastoma cells, suggesting that targeting TRIP6 may prove to be an effective strategy to restore the function of A20 and CYLD in restricting the NF-κB activity in these cancer cells."
sparser
"Nonetheless, depletion of TRIP6 by either shRNA ( xref ) or Cas9/sgRNA ( xref ) not only enhanced the association of TRAF6 with A20, but also with CYLD in untreated and treated cells, suggesting a significant role for TRIP6 in antagonizing the binding of TRAF6 to both A20 and CYLD in ovarian cancer cells."
sparser
"In this regard, here we provide evidence that the adaptor protein TRIP6 (thyroid hormone receptor-interacting protein 6), a specific interacting protein of the LPA2 receptor but not other LPA receptors, recruits TRAF6 to the LPA2 receptor and enhances the E3 ligase activity of TRAF6 by antagonizing the association of A20 and CYLD to TRAF6."
sparser
"Wild-type mouse embryonic fibroblasts (MEFs) or MEFs that lack expression of A20 ( A20 −/− ) or TAX1BP1 ( Tax1bp1 −/− ) were treated with IL-1 for various times, and the interactions between TRAF6, A20, and TAX1BP1 were monitored by immunoprecipitations and protein immunoblotting ( xref and xref )."
sparser
"We further found bavachin can increase the interaction of ubiquitin-editing enzyme A20 complex including A20, Tax1-binding protein 1 (TAX1BP1) and Itch, the subsequently downregulated the K63-ubiquitination of TNF receptor associated factor 6 (TRAF6) and NF-κB signaling pathway."
sparser
"To determine whether mutations in the myristoylation domain, PPxY motif or RING domain alter RNF11’s association with the A20 ubiquitin-editing protein complex, SH-SY5Y shRNA-RNF11 cells were transfected with vector, V5-WT R , V5-G2A R , V5-Y40A R , V5-I101A R , V5-H2 R or V5-C99A R , and co-IPs for endogenous Itch were performed."
sparser
"Our analyses revealed that (1) neuronal RNF11 acts as a negative regulator of the canonical NF-κB signaling pathway, (2) neuronal RNF11 associates with the A20 ubiquitin-editing protein complex, (3) the myristoylation and PPxY domains of RNF11 are required and necessary, respectively, for RNF11’s effects on NF-κB signaling and association with Itch, a member of the A20-ubiquitin editing protein complex and (4) reduced expression of RNF11 in neurons can result in aberrant regulation of inflammatory signaling."
E3_Ub_ligase binds Ubiquitin and TNFAIP3. 2 / 2
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eidos
"One critical finding from this study is that A20 not only completely blocked the transcription of other NF-kappaB target genes known to antagonize JNK signaling , but also effectively suppressed TNF-induced JNK activation and apoptotic cell death in NF-kappaB activation-deficient MEFs ( Figure 2 ) ."
reach
"Consistently, IEC specific deletion of TNFAIP3 (encoding A20), a gene mutated in Crohn 's disease that encodes an E3 ligase editing enzyme involved in dampening NF-kappaB signaling and TNF induced apoptosis, leads to massive IEC apoptosis and increased susceptibility to experimental colitis."
TNFAIP3 activates apoptotic process.
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reach
"Various viruses develop different strategies to limit or utilize apoptosis for benefitting their replication and persistent infection (44, 45) , PDCoV has CircRNA TNFAIP3 and Deltacoronavirus Replication ® been reported to induce caspase-dependent apoptosis during replication (46) ."
sparser
"Other loci and genes involved in inflammatory pathways that have been implicated in RA with a modest effect size include CTLA4 (negative regulator of T cell activation) ( xref ), STAT4 (transcription factor involved in intracellular cytokine signaling) ( xref ), TNFAIP3 [inhibitor of nuclear factor κ-light chain enhancer of activated B cells (NF-κB) signaling; it is required for termination of tumor necrosis factor (TNF)-induced signals] ( xref ), TRAF1-C5 (locus including TRAF1 , which encodes a negative regulator of intracellular TNF signaling that binds to TNFAIP3, and C5 , which encodes complement factor C5) ( xref ), IL2/21 [encoding interleukin (IL)-2 and IL-21] ( xref ), CD40 (surface receptor present in various immune cells, including B cells, where it is crucial for B-T cell interaction) ( xref ), IL2RA/IL2RB (encoding IL-2 receptor alpha and beta chains, respectively), ( xref , xref ) IL6R [encoding the IL-6 receptor (IL-6R)] ( xref ) or CCL21 (lymphocyte chemokine) ( xref ), among many others ( xref , xref , xref )."
reach
"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]."
reach
"In addition to IFN pathway genes, the higher anti-viral activity of hub genes related to TNF signaling and NAD metabolisms such as TNFAIP3, PARP9, and DTX3L would be able to characterize patients with a high viral load, indicating a clear association of their expression to the presence of the virus and the phase of the disease."
reach
"Although dexamethasone mediated activation of the glucocorticoid receptor (GR) potently repressed expression of IL1beta, IL8, and several other pro inflammatory TNF targets, the expression of anti-inflammatory TNF targets such as TNFAIP3 (A20) and NFKBIA was selectively spared or augmented by dexamethasone treatment."
TNFAIP3 affects inflammatory response
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eidos
"A20 Restricts Inflammatory Response and Desensitizes Gingival Keratinocytes to Apoptosis The pathophysiology of periodontal disease involves a perturbed immune system to a dysbiotic microflora leading to unrestrained inflammation , collateral tissue damage , and various systemic complications ."
eidos
"In vivo and in vitro experiments indicated that inflammation , a key characteristic of epilepsy , was inhibited by TNFAIP3 upregulation , as evidenced by the downregulated expression of pro-inflammatory cytokine interleukin ( IL ) -1 beta and inducible NO synthase ( iNOS ) , along with the decreased levels of NLRP3 inflammasome , which could activate inflammation ."
reach
"In vivo and in vitro experiments indicated that inflammation, a key characteristic of epilepsy, was inhibited by TNFAIP3 upregulation, as evidenced by the downregulated expression of pro-inflammatory cytokine interleukin (IL)-1β and inducible NO synthase (iNOS), along with the decreased levels of NLRP3 inflammasome, which could activate inflammation."
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"These are likely induced by TNFAIP3‐deficient cDC1s in the lungs; however, we cannot exclude that the IFNγ‐expressing T cells in the lung were partly induced by TNFAIP3‐deficient Langerhans cells in the skin, because skin DCs have been reported to mediate inflammation in the airways through the skin‐lung axis."
reach
"Despite this interferon response, it was shown by the authors of the study [16], that the SARS-COV-2 virus is a low inducer of the IFN-I and IFN-III systems, a failure which likely contributes to the development of COVID-19 during the viral infection.A third module (c) revolves around TNF and includes IL1A, IL1B, TNFSF14, TNFAIP3, and CSF2 that likely mediates the inflammatory response associated with COVID-19 progression."
eidos
"According with this view , we can assume that the A20 upregulation observed in sciatic nerve of 4 months old SOD1-G93A mice can be ascribed to an activation of the non-canonical pathway , fitting with the idea that A20 ( 62 ) , when aberrantly activated , in different cell types , can promote autoimmunity and inflammation ."
TNFAIP3 affects signaling
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46
"A similar functional redundancy of the A20 zinc fingers was also observed for binding of A20 to a number of other proteins, including two novel NF-kappaB inhibitory proteins (ABIN-1, ABIN-2), A20 itself, the anti-apoptotic protein TXBP151, and a regulatory component of the IkappaB kinase complex, IKKgamma."
sparser
"In contrast, RNF11 silencing did not result in increased expression of immune genes, apoptosis, or HRSV growth, indicating that this protein does not collaborate with A20 in the regulation of these processes, despite the fact that RNF11 seems to form a complex with A20, TAX1BP1, and ITCH to inhibit TNF and LPS-induced NF-κB signaling [ xref ]."
sparser
"Wild-type mouse embryonic fibroblasts (MEFs) or MEFs that lack expression of A20 ( A20 −/− ) or TAX1BP1 ( Tax1bp1 −/− ) were treated with IL-1 for various times, and the interactions between TRAF6, A20, and TAX1BP1 were monitored by immunoprecipitations and protein immunoblotting ( xref and xref )."
sparser
"Enforced expression of NEMO in cells revealed that NEMO can both promote and block NF-kappaB activation and dramatically augments the phosphorylation of c-Jun. The findings suggest that the signaling activities of the IKK signalosome are regulated through binding of NEMO to RIP and A20 within the p55 TNF receptor complex."
TNFAIP3 affects IKK_complex
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TNFAIP3 inhibits IKK_complex.
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TNFAIP3 inhibits IKK_complex. 10 / 33
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sparser
"A20 inhibition of IKK was dependent on A20 binding to NEMO which was induced by K63-linked polyubiquitin chains. xref The binding of A20 with NEMO occurred rapidly upon IL-1 stimulation (2–5 min) in HeLa cells. xref Therefore, the polyubiquitin chains that serve to activate IKK also serve a dual function in its negative regulation by the recruitment of A20 to NEMO."
TNFAIP3 binds IKK_complex.
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IKK_complex binds TNFAIP3. 5 / 5
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sparser
"The cluster C 1 contains parameters describing IKK kinase post-translational modifications and its interactions with the I κ B α -NF- κ B complex; C 2: TNF- α receptor activation and signalling; C 3: IKKK kinase post-translational modifications and its interactions with A20 and IKK; C 4: nuclear shuttling of NF- κ B and I κ B α - NF- κ B binding; C 4: A20 transcription and mRNA degradation; C 6: I κ B α transcription, translation, degradation and post-translational modifications C 7: NF- κ B - DNA interactions and nuclear shuttling of I κ B α ."
sparser
"There are at least two levels of A20-mediated regulation of IKK complex activity: (1) A20 directly interacts with the IKK complex reducing its catalytic activity xref – xref and (2) A20 primes TNF receptor interacting protein (RIP) for degradation, and thus attenuates TNF receptor downstream signaling xref ."
IKK_complex binds TBK1 and TNFAIP3. 2 / 2
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1
1
sparser
"To determine whether mutations in the myristoylation domain, PPxY motif or RING domain alter RNF11’s association with the A20 ubiquitin-editing protein complex, SH-SY5Y shRNA-RNF11 cells were transfected with vector, V5-WT R , V5-G2A R , V5-Y40A R , V5-I101A R , V5-H2 R or V5-C99A R , and co-IPs for endogenous Itch were performed."
sparser
"Our analyses revealed that (1) neuronal RNF11 acts as a negative regulator of the canonical NF-κB signaling pathway, (2) neuronal RNF11 associates with the A20 ubiquitin-editing protein complex, (3) the myristoylation and PPxY domains of RNF11 are required and necessary, respectively, for RNF11’s effects on NF-κB signaling and association with Itch, a member of the A20-ubiquitin editing protein complex and (4) reduced expression of RNF11 in neurons can result in aberrant regulation of inflammatory signaling."
sparser
"Furthermore, the results of domain mapping experiments show that A20 binds to the non-catalytic amino-terminal region of ASK1, which has been shown to be responsible for the interaction with E3 ligase-CIAP1, -TRAF2, or thioredoxin, xref , xref suggesting that the association of ASK1 through this amino-terminal region with A20 has an essential function in down-regulation of JNK signaling through regulating ASK1 stability and degradation."
sparser
"As an alternative mechanism underlying the anti-apoptotic effects of A20, Won et al proposed that A20 binds to ASK1, an important mitogen-activated protein kinase kinase (MAPKK) kinase in the JNK signaling cascade, and mediates ASK1 degradation, leading to the suppression of JNK activation and eventually the inhibition of apoptosis ( xref )."
sparser
"Another possible mechanism for the anti-apoptotic effects of A20 has been proposed by Won et al. ( xref ): A20 binds to ASK1, an important MAPKK kinase in the JNK signaling cascade, and mediates ASK1 degradation, leading to suppression of JNK activation and eventually inhibition of apoptosis (Won et al., xref )."
eidos
"A20 reduces the stability and promotes the degradation of ASK1 through the ubiquitination process A20 restricts TNF-induced NF-kappaB signaling through its ubiquitin editing activity on RIP1 ,14,15 it is thus of interest to test whether A20 would be affecting the stability of ASK1 through a similar mechanism ."
reach
"In screening for proteins that interact with ASK1 in the context of NASH, we identified the deubiquitinase tumor necrosis factor alpha induced protein 3 (TNFAIP3) as a key endogenous suppressor of ASK1 activation, and we found that TNFAIP3 directly interacts with and deubiquitinates ASK1 in hepatocytes."
"we identified the deubiquitinase tumor necrosis factor alpha-induced protein 3 (TNFAIP3) as a key endogenous suppressor of ASK1 activation, and we found that TNFAIP3 directly interacts with and deubiquitinates ASK1 in hepatocytes."
sparser
"In contrast, RNF11 silencing did not result in increased expression of immune genes, apoptosis, or HRSV growth, indicating that this protein does not collaborate with A20 in the regulation of these processes, despite the fact that RNF11 seems to form a complex with A20, TAX1BP1, and ITCH to inhibit TNF and LPS-induced NF-κB signaling [ xref ]."
sparser
"DUB-E3 interactions are used for mutual ubiquitin-dependent regulation (e.g., to control each other’s stability, see above) or for editing ubiquitin chain architecture on particular substrates (as shown for the hybrid DUB/E3 enzyme A20 and CYLD-ITCH complexes during inflammatory signaling [ xref , xref ])."
sparser
"Therefore, the interaction of A20 with cIAP1/2 may inhibit the TRAF2/TRAF3 interaction through structural changes in TRAF2 induced by the indirect interaction of A20 with TRAF2 via the BIR domains of cIAP1/2 or by the direct interaction between A20 and TRAF2, as suggested by the yeast two-hybrid experiment xref ."
sparser
"With regard to TNFR1 signaling, TRAF2 binds to the amino-terminal region of A20, and this interaction is required for the recruitment of A20 into TNFR1 signaling complex. xref , xref Therefore, it is possible that A20 may regulate JNK signaling pathway by affecting this signaling complex formation."
sparser
"In contrast, RNF11 silencing did not result in increased expression of immune genes, apoptosis, or HRSV growth, indicating that this protein does not collaborate with A20 in the regulation of these processes, despite the fact that RNF11 seems to form a complex with A20, TAX1BP1, and ITCH to inhibit TNF and LPS-induced NF-κB signaling [ xref ]."
sparser
"DUB-E3 interactions are used for mutual ubiquitin-dependent regulation (e.g., to control each other’s stability, see above) or for editing ubiquitin chain architecture on particular substrates (as shown for the hybrid DUB/E3 enzyme A20 and CYLD-ITCH complexes during inflammatory signaling [ xref , xref ])."
TNFAIP3 affects cell population proliferation
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5
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8
TNFAIP3 inhibits cell population proliferation.
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TNFAIP3 inhibits cell population proliferation. 10 / 21
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8
sparser
"Here, we report that miR-125b is upregulated, whereas A20 is downregulated in NPC tissues relative to normal nasopharyngeal mucosa (NNM); miR-125b promotes NPC cell proliferation and inhibits NPC cell apoptosis by targeting A20/NF-κB signaling pathway; A20 inhibits NPC cell proliferation, induces NPC cell apoptosis, and reduces the growth of NPC xenograft tumors."
TNFAIP3 activates cell population proliferation.
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9
TNFAIP3 activates cell population proliferation. 9 / 9
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9
reach
"However, when overexpressing TNFAIP3 and PLAU or upon activation of the NFkappaB pathway, all the inhibitory effects of SFE were reversed (XREF_FIG A-D), suggesting that SFE blocked the p65 promotion of TNFAIP3 and PLAU expression to inhibit ESCC cell proliferation and metastasis."
sparser
"Bioprocess. (2021) 8:65 intermediates with three disulfide bonds have been identified and may interconvert via disulfide rearrangements (Qiao et al. 2003; Hua et al. 2002) , the formation of the A20-B19 disulfide bridge appears to be the key step in refolding process and is critical to maintain the native structure of the proinsulin (Guo et al. 2008; Qiao et al. 2006 )."
sparser
"Therefore, the interaction of A20 with cIAP1/2 may inhibit the TRAF2/TRAF3 interaction through structural changes in TRAF2 induced by the indirect interaction of A20 with TRAF2 via the BIR domains of cIAP1/2 or by the direct interaction between A20 and TRAF2, as suggested by the yeast two-hybrid experiment xref ."
sparser
"With regard to TNFR1 signaling, TRAF2 binds to the amino-terminal region of A20, and this interaction is required for the recruitment of A20 into TNFR1 signaling complex. xref , xref Therefore, it is possible that A20 may regulate JNK signaling pathway by affecting this signaling complex formation."
sparser
"Insulin is a 51-amino acid peptide connected by two separate chains and three disulfide bonds (one intra-chain, A6-A11 and two inter-chain, A7-B7 & A20-B19). xref Ever since its discovery in 1921, insulin has been the mainstay for the treatment of type 1 diabetes and late-stage type 2 diabetes. xref Rapid- and long-acting insulin analogs have been developed over the past decades to achieve better blood glucose control. xref However, these analogs still suffer from the undesired properties of native insulin such as propensity of degradation, fibrillation, and disulfide scrambling, which makes them difficult for storage and transport, particularly in circumstances where refrigeration is challenging. xref Therefore, the development of novel insulin analogs with enhanced stability and without the need of cold-chain delivery is highly desired. xref "
Lipopolysaccharide affects TNFAIP3
11
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Lipopolysaccharide increases the amount of TNFAIP3.
8
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Lipopolysaccharide increases the amount of TNFAIP3. 10 / 14
8
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6
reach
"In this study, LJF significantly inhibited the LPS stimulated downregulation of CXCL2, CXCL1, CXCL6, NFKBIA, IFNG, IL6, IL17A, IL17F, IL17C, MMP9, and TNFAIP3 mRNA expression in lung tissue homogenates according to RNA-Seq and qRT-PCR, which indicates that the IL-17 signalling pathway is critical for treatment by LJF of LPS induced ALI."
| PMC
Lipopolysaccharide activates TNFAIP3.
1
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Lipopolysaccharide activates TNFAIP3. 8 / 8
1
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reach
"The LPS induced immune markers, specifically TLR4, TNF alpha induced protein 3 (TNFAIP3) and interleukin-1 receptor associated kinase like 2 (IRAK2), were identified among the strongest variables of the PC1, along with the increase in expression of genes related to mitochondrial metabolism (e.g. NADH dehydrogenase (ubiquinone) 1 beta sub-complex 5; NDUFB5)."
Lipopolysaccharide decreases the amount of TNFAIP3.
2
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eidos
"Thus , A20 deficiency in mice triggers inflammation and autoimmune disorders and might eventually lead to death.13 , 14 , 15 , 16 Many studies have reported that A20 overexpression in human periodontal ligament cells ( hPDLCs ) decreases RANKL-induced osteoclastogenesis in mouse bone marrow-derived macrophages ( BMMs ) and that A20 can inhibit autophagy through limiting the K63-linkage ubiquitination of TRAF6 , or by directly deubiquitinating Beclin1.17 , 18 Numerous studies have shown that periodontal tissues are in a hypoxic microenvironment during periodontitis ."
eidos
"It has been reported that K48-linked polyubiquitin chains promoted the degradation of proteasome , while K63-linked polyubiquitin chains mediate ubiquitination.22 Thus , these results showed that A20 may suppress autophagy through promoting the degradation of TRAF6 and inhibiting the ubiquitination of TRAF6 ."
sparser
"Furthermore, the results of domain mapping experiments show that A20 binds to the non-catalytic amino-terminal region of ASK1, which has been shown to be responsible for the interaction with E3 ligase-CIAP1, -TRAF2, or thioredoxin, xref , xref suggesting that the association of ASK1 through this amino-terminal region with A20 has an essential function in down-regulation of JNK signaling through regulating ASK1 stability and degradation."
sparser
"As an alternative mechanism underlying the anti-apoptotic effects of A20, Won et al proposed that A20 binds to ASK1, an important mitogen-activated protein kinase kinase (MAPKK) kinase in the JNK signaling cascade, and mediates ASK1 degradation, leading to the suppression of JNK activation and eventually the inhibition of apoptosis ( xref )."
sparser
"Another possible mechanism for the anti-apoptotic effects of A20 has been proposed by Won et al. ( xref ): A20 binds to ASK1, an important MAPKK kinase in the JNK signaling cascade, and mediates ASK1 degradation, leading to suppression of JNK activation and eventually inhibition of apoptosis (Won et al., xref )."
TNFAIP3 affects activity
|
20
sparser
"On the other hand, TNFAIP3 can inhibit TLR-induced activity of NF κ B by de-ubiquitination of TRAF6. xref Interestingly, also IRAK1 has been associated with risk for SLE, xref and because SNPs in the TRAF6 region and in TNFAIP3 have also been associated with risk for RA, xref , xref , xref it seems as variants of all these genes have the potential to contribute to loss of tolerance and autoimmune reactions."
sparser
"Nonetheless, depletion of TRIP6 can significantly enhance the association of A20 or CYLD with TRAF6 in ovarian cancer cells and promote the binding of A20 to TRAF6 in glioblastoma cells, suggesting that targeting TRIP6 may prove to be an effective strategy to restore the function of A20 and CYLD in restricting the NF-κB activity in these cancer cells."
sparser
"Nonetheless, depletion of TRIP6 by either shRNA ( xref ) or Cas9/sgRNA ( xref ) not only enhanced the association of TRAF6 with A20, but also with CYLD in untreated and treated cells, suggesting a significant role for TRIP6 in antagonizing the binding of TRAF6 to both A20 and CYLD in ovarian cancer cells."
sparser
"In this regard, here we provide evidence that the adaptor protein TRIP6 (thyroid hormone receptor-interacting protein 6), a specific interacting protein of the LPA2 receptor but not other LPA receptors, recruits TRAF6 to the LPA2 receptor and enhances the E3 ligase activity of TRAF6 by antagonizing the association of A20 and CYLD to TRAF6."
sparser
"DUB-E3 interactions are used for mutual ubiquitin-dependent regulation (e.g., to control each other’s stability, see above) or for editing ubiquitin chain architecture on particular substrates (as shown for the hybrid DUB/E3 enzyme A20 and CYLD-ITCH complexes during inflammatory signaling [ xref , xref ])."
sparser
"Several DUBs, including A20, CYLD and USP7, have been reported to downregulate NF- κ B. Co-IP assays were thus carried out to examine the interactions between these enzymes and HSCARG, and the results showed that HSCARG interacts weakly with A20 or CYLD but strongly interacts with USP7 ( xref , xref )."
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6
sparser
"These functions of A20 in liver injury and HCC imply that TNFAIP3 polymorphisms associated with the attenuation of A20 expression and/or the interference of A20 function, such as the TT > A variant investigated in this study, may be associated with disease progression and HCC development in chronic HBV infection."
TNFAIP3 affects Arthritis, Rheumatoid
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TNFAIP3 binds Arthritis, Rheumatoid.
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TNFAIP3 binds Arthritis, Rheumatoid. 8 / 8
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sparser
"For example, the association of TNFAIP3 with RA risk reached genome-wide levels of significance in this expansion of the WTCCC analysis, and the robustly validated locus STAT4 , for which no significant association had been found in the original WTCCC study, was found to be associated with RA in the present study ( xref )."
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TNFAIP3 binds OLIG3 and Arthritis, Rheumatoid. 2 / 2
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sparser
"This association locus was first identified in a GWAS xref and has been subsequently confirmed in multiple Caucasian and Asian cohorts. xref – xref Specifically, a study of 3962 RA patients and 3531 healthy controls demonstrated strong association (OR = 1.2; 95% CI: 1.1–1.3; P = 2.6 × 10 6 ) with a variant (rs6920220) in an intergenic region of chromosome 6q23 region between oligodendrocyte linear transcription factor 3 ( OLIG3 ) and TNF-α-induced protein 3 ( TNFAIP3 ). xref The validity of this study has been confirmed by a recent meta-analysis of seven studies investigating the association of the TNFAIP3-OLIG3 region with RA, which indicated a strong association of the variant rs6920220 (OR = 1.2, 95% CI: 1.2–1.3; P = 7.9 × 10 −17 ). xref Since the TNFAIP3 gene acts as a negative regulator of the transcription factor nuclear factor-κB (NFκB) in response to TNF- and toll-like receptor activation, xref , xref it is an attractive RA susceptibility candidate gene."
TNFAIP3 binds TRAF1 and Arthritis, Rheumatoid. 2 / 2
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2
TNFAIP3 inhibits Arthritis, Rheumatoid.
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2
TNFAIP3 activates Arthritis, Rheumatoid.
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2
Polyubiquitin affects TNFAIP3
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17
sparser
"Accumulating data from several retrospective analyses [ xref , xref , xref , xref , xref , xref ] and the randomized phase 3 study ALTA-1L [ xref ] show that the “short” EML4-ALK fusion variant 3 (E6:A20, xref b) is associated with earlier treatment failure and shorter survival regardless of the type of treatment."
sparser
"Revealing coexistence of double ALK fusion: EML4 - ALK (E6:A20, MAF = 24.7%) and ALK - SSH2 (A19:S3, MAF = 0.85%) (Fig. xref B), which was further validated by another NGS 10 cancer‐related gene panel (RNA-based detection for fusion genes, Amoy Diagnostics, Xiamen, China), EML4 - ALK ALK - SSH2 (E6:A20, MAF = 25.6%; A19:S3, MAF = 0.68%, respectively) (Fig. xref C)."
sparser
"In terms of EML4 - ALK rearrangement, the most common variant was variant 1 (E13:A20), which accounted for 37.1% of patients (49/132), followed by variant 3a/b (E6:A20) and variant 2 (E20:A20), which accounted for 30.3% (40/132) and 11.4% of patients (15/132), respectively ( xref )."
TNFAIP3 affects expression
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14
sparser
"These results demonstrate that A20 inhibits NF-kappaB-dependent gene expression by interfering with a novel TNF-induced and RIP- or TRAF2-mediated pathway that is different from the NIK-IkappaB kinase pathway and that is specifically involved in the transactivation of NF-kappaB."
sparser
"Therefore, the inhibition of NF-κB– dependent gene expression by A20 cannot be explained by an A20-induced alteration in the subunits of NF-κB. xref showed recently that A20 acts upstream of IκB degradation and prevented the nuclear translocation of NF-κB. The reason for the discrepancy with our results is still unclear."
sparser
"Here we show that A20 inhibits TNF-induced NF-κB–dependent gene expression by interfering with a TRAF2-mediated signaling pathway that is different from the NIK–IκB or the p38 MAP kinase pathway, and which is specifically involved in the transactivation of NF-κB. Furthermore, we demonstrate that the A20 binding inhibitor of NF-κB activation (ABIN), a protein that interacts with the functional COOH-terminal part of A20, has similar NF-κB inhibiting effects as A20, suggesting that A20 can inhibit NF-κB activation via its interaction with ABIN."
Arthritis, Rheumatoid affects TNFAIP3
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TNFAIP3 binds Arthritis, Rheumatoid. 8 / 8
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7
sparser
"For example, the association of TNFAIP3 with RA risk reached genome-wide levels of significance in this expansion of the WTCCC analysis, and the robustly validated locus STAT4 , for which no significant association had been found in the original WTCCC study, was found to be associated with RA in the present study ( xref )."
|
2
TNFAIP3 binds OLIG3 and Arthritis, Rheumatoid. 2 / 2
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2
sparser
"This association locus was first identified in a GWAS xref and has been subsequently confirmed in multiple Caucasian and Asian cohorts. xref – xref Specifically, a study of 3962 RA patients and 3531 healthy controls demonstrated strong association (OR = 1.2; 95% CI: 1.1–1.3; P = 2.6 × 10 6 ) with a variant (rs6920220) in an intergenic region of chromosome 6q23 region between oligodendrocyte linear transcription factor 3 ( OLIG3 ) and TNF-α-induced protein 3 ( TNFAIP3 ). xref The validity of this study has been confirmed by a recent meta-analysis of seven studies investigating the association of the TNFAIP3-OLIG3 region with RA, which indicated a strong association of the variant rs6920220 (OR = 1.2, 95% CI: 1.2–1.3; P = 7.9 × 10 −17 ). xref Since the TNFAIP3 gene acts as a negative regulator of the transcription factor nuclear factor-κB (NFκB) in response to TNF- and toll-like receptor activation, xref , xref it is an attractive RA susceptibility candidate gene."
TNFAIP3 binds TRAF1 and Arthritis, Rheumatoid. 2 / 2
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2
reach
"In contrast, IL-1 strongly stimulated the recruitment of p65 to 5 of the 8 genomic regions that contained genes shown to be regulated at the mRNA and transcriptional level by both HCoV-229E and IL-1 (see above and Fig 5D) whereas, for HCoV-229E-infected cells, only a moderate increase of p65 binding to the CXCL2, CXCL1, TNFAIP3 and IL8 loci could be detected (Fig 5D)."
reach
"After verifying that SFE could increase the content of p65 bound to IkappaBalpha and inhibit p65 from entering the nuclear to inactivate the NFkappaB pathway (XREF_FIG D, Supplementary Figure S7B), we further identified the inhibitory effect of SFE on p65 binding to TNFAIP3 and PLAU, which can be reversed by LPS treatment, analyzed by ChIP-PCR and luciferase reporter assays (XREF_FIG E, Supplementary Figure S8A)."
eidos
"To further dissect these findings , siRNAs were transfected into cells to knock down the transcription factor p65 in the presence of Casp8 , and the Western blot results indicated that decreased p65 impeded A20 expression ( Figure 3G , lane 1 and lane 3 ) and abrogated Casp8-induced A20 upregulation ( Figure 3G , lanes 1-4 ; Figure S3D ) ."
TNFAIP3 affects Lupus Erythematosus, Systemic
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12
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10
sparser
"Independent genetic associations of SLE and TNFAIP3 in European-ancestry (EA) subjects have been localized to a region 185 kb upstream of TNFAIP3 that was first identified with rheumatoid arthritis xref , xref , a region 249 kb downstream of TNFAIP3 and a 109 kb haplotype that spans the TNFAIP3 coding region xref – xref that includes a suggested causal coding variant in exon 3 (rs2230926 T>G; F127C, RefSeq: NP_006281.1) that reduces the ability of A20 to attenuate NF-κB signaling xref ."
sparser
"As shown in xref , SNPs within BLK (rs2736340 [ P = 4.25 × 10 –6 , odds ratio (OR) 1.48, 95% confidence interval (95% CI) 1.25–1.75], rs13277113 [ P = 7.34 × 10 –6 , OR 1.45, 95% CI 1.23– 1.71]), TNFSF4 (rs2205960 [ P = 2.82 × 10 –5 , OR 1.39, 95% CI 1.19–1.62], rs10489265 [ P = 3.10 × 10 –4 , OR 1.33, 95% CI 1.14–1.55]), and TNFAIP3 (rs5029939 [ P = 1.92 × 10 –3 , OR 1.58, 95% CI 1.18–2.12]) were associated with SLE at both the allele and genotype levels."
sparser
"In order to examine whether TNFAIP3 is associated with SLE in Chinese Han population, we genotyped one of its non-synonymous mutation SNP rs2230926, showing significant association evidence with SLE in European population, with 1,420 cases and 4,461 controls of Chinese Han by using Sequenom MassArray system."
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2
reach
"However, a consistent tendency toward a gene gene interaction between BLK and TNFAIP3 (P < 0.05), TNFSF4 and TNFAIP3 (P < = 0.05), and TNFSF4 and TRAF1 (for rs10818488 x rs2205960, P = 0.05 in Chinese; for rs10818488 x rs10489265, P = 0.08 in Chinese [versus P = 0.10 in Caucasians]) was observed in both Chinese and Caucasians."
sparser
"However, a consistent tendency toward a gene–gene interaction between BLK and TNFAIP3 ( P < 0.05), TNFSF4 and TNFAIP3 ( P ≤ 0.05), and TNFSF4 and TRAF1 (for rs10818488 × rs2205960, P = 0.05 in Chinese; for rs10818488 × rs10489265, P = 0.08 in Chinese [versus P = 0.10 in Caucasians]) was observed in both Chinese and Caucasians."
sparser
"In contrast, RNF11 silencing did not result in increased expression of immune genes, apoptosis, or HRSV growth, indicating that this protein does not collaborate with A20 in the regulation of these processes, despite the fact that RNF11 seems to form a complex with A20, TAX1BP1, and ITCH to inhibit TNF and LPS-induced NF-κB signaling [ xref ]."
Lupus Erythematosus, Systemic affects TNFAIP3
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12
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10
sparser
"Independent genetic associations of SLE and TNFAIP3 in European-ancestry (EA) subjects have been localized to a region 185 kb upstream of TNFAIP3 that was first identified with rheumatoid arthritis xref , xref , a region 249 kb downstream of TNFAIP3 and a 109 kb haplotype that spans the TNFAIP3 coding region xref – xref that includes a suggested causal coding variant in exon 3 (rs2230926 T>G; F127C, RefSeq: NP_006281.1) that reduces the ability of A20 to attenuate NF-κB signaling xref ."
sparser
"As shown in xref , SNPs within BLK (rs2736340 [ P = 4.25 × 10 –6 , odds ratio (OR) 1.48, 95% confidence interval (95% CI) 1.25–1.75], rs13277113 [ P = 7.34 × 10 –6 , OR 1.45, 95% CI 1.23– 1.71]), TNFSF4 (rs2205960 [ P = 2.82 × 10 –5 , OR 1.39, 95% CI 1.19–1.62], rs10489265 [ P = 3.10 × 10 –4 , OR 1.33, 95% CI 1.14–1.55]), and TNFAIP3 (rs5029939 [ P = 1.92 × 10 –3 , OR 1.58, 95% CI 1.18–2.12]) were associated with SLE at both the allele and genotype levels."
sparser
"In order to examine whether TNFAIP3 is associated with SLE in Chinese Han population, we genotyped one of its non-synonymous mutation SNP rs2230926, showing significant association evidence with SLE in European population, with 1,420 cases and 4,461 controls of Chinese Han by using Sequenom MassArray system."
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2
sparser
"In contrast, RNF11 silencing did not result in increased expression of immune genes, apoptosis, or HRSV growth, indicating that this protein does not collaborate with A20 in the regulation of these processes, despite the fact that RNF11 seems to form a complex with A20, TAX1BP1, and ITCH to inhibit TNF and LPS-induced NF-κB signaling [ xref ]."
reach
"However, a consistent tendency toward a gene gene interaction between BLK and TNFAIP3 (P < 0.05), TNFSF4 and TNFAIP3 (P < = 0.05), and TNFSF4 and TRAF1 (for rs10818488 x rs2205960, P = 0.05 in Chinese; for rs10818488 x rs10489265, P = 0.08 in Chinese [versus P = 0.10 in Caucasians]) was observed in both Chinese and Caucasians."
sparser
"However, a consistent tendency toward a gene–gene interaction between BLK and TNFAIP3 ( P < 0.05), TNFSF4 and TNFAIP3 ( P ≤ 0.05), and TNFSF4 and TRAF1 (for rs10818488 × rs2205960, P = 0.05 in Chinese; for rs10818488 × rs10489265, P = 0.08 in Chinese [versus P = 0.10 in Caucasians]) was observed in both Chinese and Caucasians."
sparser
"To determine whether mutations in the myristoylation domain, PPxY motif or RING domain alter RNF11’s association with the A20 ubiquitin-editing protein complex, SH-SY5Y shRNA-RNF11 cells were transfected with vector, V5-WT R , V5-G2A R , V5-Y40A R , V5-I101A R , V5-H2 R or V5-C99A R , and co-IPs for endogenous Itch were performed."
sparser
"Our analyses revealed that (1) neuronal RNF11 acts as a negative regulator of the canonical NF-κB signaling pathway, (2) neuronal RNF11 associates with the A20 ubiquitin-editing protein complex, (3) the myristoylation and PPxY domains of RNF11 are required and necessary, respectively, for RNF11’s effects on NF-κB signaling and association with Itch, a member of the A20-ubiquitin editing protein complex and (4) reduced expression of RNF11 in neurons can result in aberrant regulation of inflammatory signaling."
sparser
"Mutation of the catalytic cysteine residue 103 in the OTU domain also abrogates A20 binding with Ubc13 and UbcH5c. xref The crystal structure of the A20 OTU domain reveals that cysteine 103 resides within an alpha helix domain that contributes to ubiquitin binding. xref Therefore, both the OTU domain and ZnF4 may coordinate interactions with ubiquitin, E2 enzymes and adaptor molecules such as TAX1BP1."
sparser
"Although wild-type A20 interacted with endogenous Ubc13 and UbcH5c in cells stimulated with LPS or IL-1, both A20 C103A and A20 ZnF4 mutants were defective for binding to Ubc13 and UbcH5c ( xref ) and thus were unable to inhibit TRAF6 ubiquitination or promote Ubc13 degradation ( xref )."
sparser
"HTLV-1 Tax might also provide a bridge to the proteasome by disrupting the interaction between an E3 ubiquitin ligase and its substrate, illustrated by the inactivation by Tax of the A20-Itch E3 ligase complex, potentially leading to a permanent activation of tumor necrosis factor (TNF) receptor (TNFR) signaling [ xref ]."
sparser
"TAX 1 BP 1 is a critical adaptor molecule for the A20 enzyme complex and is essential for the negative regulation of the canonical NF-κB pathway [ xref , xref , xref ], thus prompting us to examine whether CADM1 is required for Tax to target TAX 1 BP 1 phosphorylation and inactivation of the A20 complex."
sparser
"Mutation of the catalytic cysteine residue 103 in the OTU domain also abrogates A20 binding with Ubc13 and UbcH5c. xref The crystal structure of the A20 OTU domain reveals that cysteine 103 resides within an alpha helix domain that contributes to ubiquitin binding. xref Therefore, both the OTU domain and ZnF4 may coordinate interactions with ubiquitin, E2 enzymes and adaptor molecules such as TAX1BP1."
sparser
"Although wild-type A20 interacted with endogenous Ubc13 and UbcH5c in cells stimulated with LPS or IL-1, both A20 C103A and A20 ZnF4 mutants were defective for binding to Ubc13 and UbcH5c ( xref ) and thus were unable to inhibit TRAF6 ubiquitination or promote Ubc13 degradation ( xref )."
reach
"At this time, very little information is available regarding the interaction of TNFAIP3 and STAT3 activation, and what is there appears disease and tissue dependent : in liver, TNFAIP3 activity results in increased STAT3 phosphorylation and IL-6 induction via inhibition of suppressor of cytokine signaling 3."
reach
"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)."
reach
"Using the MWCL-A20 and HBL-1-A20 , we were able to show that loss of TNFAIP3 enhances MYD88 -driven NF-κB and p38 signaling resulting in increased expression of NF-κB target genes IL-6 and CXCL10, known NF-κB target genes , have both been shown to be significantly upregulated in WM and DLBCL, and higher serum levels correlate with an inferior survival ."
reach
"The variant proximal to NFkappaB1 controls signaling responses by altering the expression of NFkappaB itself, with the GG risk genotype expressing 20-fold more p50 NFkappaB and diminished expression of the negative regulators of the NFkappaB pathway : TNFalpha induced protein 3 (TNFAIP3), B cell leukemia 3 (BCL3), and cellular inhibitor of apoptosis 1 (CIAP1)."
reach
"At least 36 different loci have been identified as susceptibility loci of psoriasis by GWAS [XREF_BIBR], including the TNIP1 gene, which encodes TNF-alpha-induced protein 3 interacting protein 1 (TNIP1), as well as the tumor necrosis factor alpha induced protein 3 (TNFAIP3) gene, which encodes protein A20 [XREF_BIBR, XREF_BIBR]."
reach
"Other potential hubs includes TRAF6 (TNF receptor associated factor 6), PIN1 (Peptidyl-prolyl cis-trans isomerase NIMA interacting 1), FOS (FBJ murine osteosarcoma viral oncogene homolog), CTNNB1 (Catenin (cadherin associated protein) beta 1), CDKN1A (Cyclin dependent kinase inhibitor 1A (P21, Cip1)-A), TNFAIP3 (Tumor necrosis factor, alpha induced protein 3), SIRT1 (Sirtuin 1), ESR1 (Estrogen receptor 1) and HDAC5 (Histone deacetylase 5)."
sparser
"To determine whether mutations in the myristoylation domain, PPxY motif or RING domain alter RNF11’s association with the A20 ubiquitin-editing protein complex, SH-SY5Y shRNA-RNF11 cells were transfected with vector, V5-WT R , V5-G2A R , V5-Y40A R , V5-I101A R , V5-H2 R or V5-C99A R , and co-IPs for endogenous Itch were performed."
sparser
"Our analyses revealed that (1) neuronal RNF11 acts as a negative regulator of the canonical NF-κB signaling pathway, (2) neuronal RNF11 associates with the A20 ubiquitin-editing protein complex, (3) the myristoylation and PPxY domains of RNF11 are required and necessary, respectively, for RNF11’s effects on NF-κB signaling and association with Itch, a member of the A20-ubiquitin editing protein complex and (4) reduced expression of RNF11 in neurons can result in aberrant regulation of inflammatory signaling."
reach
"As TNFAIP3 normally restricts inflammatory TLR signals and its expression is induced in a variety of tissue types XREF_BIBR, XREF_BIBR, XREF_BIBR, the increased gut permeability in TNFAIP3 -/- mice might reflect an indirect effect of ongoing inflammation in these mice, a direct role for TNFAIP3 in IEC TJ stability, or a combination of these two effects."
sparser
"As mentioned earlier, Tnfaip3 −/− mice develop spontaneous multi-organ inflammation that leads to premature lethality. xref Tnfaip3 −/− mice on a Rag1 −/− background still developed spontaneous inflammation, indicating that adaptive lymphocytes were not essential for the uncontrolled inflammatory response, xref although hematopoietic cells were clearly involved. xref Signals from TNF were similarly dispensable for the inflammation in Tnfaip3 −/− mice, and A20 potently inhibited TLR signaling in macrophages. xref Consistent with these observations, homeostatic TLR signaling dependent on the Myd88 adaptor was dysregulated in A20-deficient mice. xref The homeostatic Myd88-dependent signals were derived from commensal intestinal bacteria since treatment of Tnfaip3 −/− mice with broad spectrum antibiotics reduced systemic inflammation and prevented cachexia. xref A20 is therefore a critical regulator of immune homeostasis and TLR signaling in vivo ."
eidos
"TNFAIP3 ( A20 ) and NFKBIA regulate NF-kB activation , downregulating TLR signals , and cytokine production.29-31 Analysis of RNA-seq data of HMCs before and after dFB co-culture for the same 22 genes with DE in the FANTOM5 set revealed that most of the modulated genes were similarly altered in our mRNA-seq analysis ( Figure 6B ) ."
reach
"Indeed, these 3 genes encodes for negative regulators of NF-κB signaling pathway: IL-1 receptor-associated kinase 3 (IRAK3) inhibits IRAK1/4 at the MyD88 complex; Tnfaip3 codes for the deubiquitinase A20, which removes poly-ubiquitin chains from TNF receptor-associated factor 6 (TRAF6); TRAF1 interferes with the linear ubiquitination of NEMO by the LUBAC complex.Several signaling molecules downstream of BCR synergize with TLR pathways to modulate the TLR response."
TNFAIP3 affects E3_Ub_ligase
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sparser
"However, it is uncertain whether the E3 ligase activity associated with A20 is intrinsic, because Itch E3 ligase can be recruited to A20 via TAX1BP1 (TAX1-binding protein 1), an adaptor that was originally found to associate with the Tax protein encoded by human T-cell leukemia virus type I [ xref ]."
sparser
"It is important to note, however, that the A20-mediated K48-linked ubiquitylation and degradation of RIP1 might involve a more complex mechanism, as this function of A20 also requires ITCH (itchy homologue E3 ubiquitin protein ligase), a K48-specific E3 ligase that stably associates with A20 (Ref. xref )."
sparser
"Differential regulation of TRAF3 and Peli1, both essential E3 ubiquitin ligases facilitating TRIF-dependent signaling, was observed between wt and bid −/− microglia and astrocytes. bid deficiency resulted in increased A20-E3 ubiquitin ligase protein interactions in glia, specifically A20-TRAF6 and A20-TRAF3, implicating enhanced de-ubiquitination as the mechanism of action by which E3 ligase activity is perturbed."
E3_Ub_ligase binds Ubiquitin and TNFAIP3. 2 / 2
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sparser
"The M1-Ub chains also interact with A20 and A20-binding inhibitor of NF-κB1 (ABIN1), which restrict activation of the TAK1 and IKK complexes and so prevent the overproduction of proinflammatory cytokines and chemokines during TLR signaling that can cause lupus and other autoimmune diseases (reviewed in ref. xref )."
IKK_complex affects TNFAIP3
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IKK_complex binds TNFAIP3.
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IKK_complex binds TNFAIP3. 5 / 5
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sparser
"The cluster C 1 contains parameters describing IKK kinase post-translational modifications and its interactions with the I κ B α -NF- κ B complex; C 2: TNF- α receptor activation and signalling; C 3: IKKK kinase post-translational modifications and its interactions with A20 and IKK; C 4: nuclear shuttling of NF- κ B and I κ B α - NF- κ B binding; C 4: A20 transcription and mRNA degradation; C 6: I κ B α transcription, translation, degradation and post-translational modifications C 7: NF- κ B - DNA interactions and nuclear shuttling of I κ B α ."
sparser
"There are at least two levels of A20-mediated regulation of IKK complex activity: (1) A20 directly interacts with the IKK complex reducing its catalytic activity xref – xref and (2) A20 primes TNF receptor interacting protein (RIP) for degradation, and thus attenuates TNF receptor downstream signaling xref ."
IKK_complex binds TBK1 and TNFAIP3. 2 / 2
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IKK_complex phosphorylates TNFAIP3.
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E3_Ub_ligase affects TNFAIP3
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E3_Ub_ligase binds TNFAIP3. 8 / 8
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sparser
"However, it is uncertain whether the E3 ligase activity associated with A20 is intrinsic, because Itch E3 ligase can be recruited to A20 via TAX1BP1 (TAX1-binding protein 1), an adaptor that was originally found to associate with the Tax protein encoded by human T-cell leukemia virus type I [ xref ]."
sparser
"It is important to note, however, that the A20-mediated K48-linked ubiquitylation and degradation of RIP1 might involve a more complex mechanism, as this function of A20 also requires ITCH (itchy homologue E3 ubiquitin protein ligase), a K48-specific E3 ligase that stably associates with A20 (Ref. xref )."
sparser
"Differential regulation of TRAF3 and Peli1, both essential E3 ubiquitin ligases facilitating TRIF-dependent signaling, was observed between wt and bid −/− microglia and astrocytes. bid deficiency resulted in increased A20-E3 ubiquitin ligase protein interactions in glia, specifically A20-TRAF6 and A20-TRAF3, implicating enhanced de-ubiquitination as the mechanism of action by which E3 ligase activity is perturbed."
E3_Ub_ligase binds Ubiquitin and TNFAIP3. 2 / 2
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TNFAIP3 affects cell death
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TNFAIP3 inhibits cell death. 9 / 9
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sparser
"We considered two major hypotheses, how the increased NF-κB activation of A20-deficient pathogen-specific CD8 + T cells might cause reduced numbers of T EM and T CM : (i) A20 regulates the development of SLEC and MPEC CD8 + T cells, and (ii) A20 inhibits cell death and enables persistence of CD8 + T cells."
sparser
"Given that A20 inhibits T effector cell death in CD4 + T cells, unleashing T effector cell–mediated inflammatory activity, our data complement the picture of A20 as a potent regulator of T cell–mediated inflammation, inducing T effector cell survival while reducing T reg cell generation."
eidos
"While the cell biological mechanisms by which A20 restricts cell death remain incompletely understood , some clues are provided by the observations that several death signaling proteins undergo physiological ubiquitination , and ubiquitinated death signaling complexes are dependent upon A20 ."
sparser
"At this time, very little information is available regarding the interaction of TNFAIP3 and STAT3 activation, and what is there appears disease/tissue dependent: in liver, TNFAIP3 activity results in increased STAT3 phosphorylation and IL-6 induction via inhibition of suppressor of cytokine signaling 3 ( xref )."
sparser
"Conspicuously, 13 of the 1715 upregulated proteins and 3 of the 264 downregulated proteins were enlisted in A20-interacted proteins ( xref ; xref ), among which prohibitin (PHB) had been previously reported as a regulator of STAT3 phosphorylation. xref Afterwards, we performed co-IP assay by precipitating STAT3, A20 and PHB in cell lysate respectively, and confirmed that PHB directly interacted with A20 and STAT3 ( xref )."
TNFAIP3 affects Neoplasm Invasiveness
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TNFAIP3 inhibits Neoplasm Invasiveness.
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TNFAIP3 activates Neoplasm Invasiveness.
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sparser
"To determine whether mutations in the myristoylation domain, PPxY motif or RING domain alter RNF11’s association with the A20 ubiquitin-editing protein complex, SH-SY5Y shRNA-RNF11 cells were transfected with vector, V5-WT R , V5-G2A R , V5-Y40A R , V5-I101A R , V5-H2 R or V5-C99A R , and co-IPs for endogenous Itch were performed."
sparser
"Our analyses revealed that (1) neuronal RNF11 acts as a negative regulator of the canonical NF-κB signaling pathway, (2) neuronal RNF11 associates with the A20 ubiquitin-editing protein complex, (3) the myristoylation and PPxY domains of RNF11 are required and necessary, respectively, for RNF11’s effects on NF-κB signaling and association with Itch, a member of the A20-ubiquitin editing protein complex and (4) reduced expression of RNF11 in neurons can result in aberrant regulation of inflammatory signaling."
sparser
"Their risk-associated alleles synergistically elevate SLE susceptibility in both multivariate logistic regression analysis (OR interaction = 1.6, P = 0.0028) and genotype-stratified analysis (OR interaction = 2.4), confirming the synergistic TNFAIP3-UBE2L3 interaction in SLE risk."
sparser
"A multivariate logistic regression analysis with their interaction term according to a multiplicative model [ xref ] showed a synergistic interaction with the two SNPs (OR int = 1.6, P = 0.0028), indicating a synergistic interaction between TNFAIP3 and UBE2L3 genes in conferring SLE risk."
TNFAIP3 affects cytokine production
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TNFAIP3 inhibits cytokine production.
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TNFAIP3 inhibits cytokine production. 6 / 6
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sparser
"Porphyromonas gingivalis (P. gingivalis) , one of the keystone periodontal bacteria, can activate NF-κB signaling in macrophages and induce A20 expression in vivo when injected intraperitoneal cavity of mice and therefore it is included as a model oral bacteria in in vitro assays. ( xref ) Our results revealed that A20 inhibits pro-inflammatory cytokine production both in human and mouse macrophages infected with P. gingivalis through its effect on NF-κB signaling."
TNFAIP3 activates cytokine production.
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2
sparser
"Their risk-associated alleles synergistically elevate SLE susceptibility in both multivariate logistic regression analysis (OR interaction = 1.6, P = 0.0028) and genotype-stratified analysis (OR interaction = 2.4), confirming the synergistic TNFAIP3-UBE2L3 interaction in SLE risk."
sparser
"A multivariate logistic regression analysis with their interaction term according to a multiplicative model [ xref ] showed a synergistic interaction with the two SNPs (OR int = 1.6, P = 0.0028), indicating a synergistic interaction between TNFAIP3 and UBE2L3 genes in conferring SLE risk."
sparser
"The M1-Ub chains also interact with A20 and A20-binding inhibitor of NF-κB1 (ABIN1), which restrict activation of the TAK1 and IKK complexes and so prevent the overproduction of proinflammatory cytokines and chemokines during TLR signaling that can cause lupus and other autoimmune diseases (reviewed in ref. xref )."
sparser
"Conserved domain analysis revealed that two PtSAPs (-14 and -17) included one AN1 domain (AN1); PtSAP3 contained one A20 domain (A20); PtSAP13 contained two AN1 domains (AN1–AN1); PtSAP8 contained two AN1 domain, and two CH2–CH2 domains (AN1–AN1–CH2–CH2); and the remaining 14 SAP members included one A20 domain and one AN1 domain (A20–AN1) ( xref , xref and xref )."
sparser
"When we compared the expression patterns of A20-AN1 and AN1 castor bean SAP genes, we found that SAP genes of the same type did not exhibit similar expression patterns, suggesting that transcriptional regulation of castor bean SAP genes of the same type might vary in response to stresses."
Infections affects TNFAIP3
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Infections increases the amount of TNFAIP3.
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Infections increases the amount of TNFAIP3. 6 / 6
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reach
"Both OSU and NCDV NSP1 interact with β-TrCP, indicating that an association between NSP1 and target is likely necessary to induce turnover, as is true for NSP1 proteins that mediate IRF3 degradation.Recently, microarray analysis of host gene expression in HT-29 (human colorectal adenocarcinoma) cells has demonstrated that infection with SA11-4F, Wa, or bovine A5-13 RVA upregulates transcription of the tumor necrosis factor (TNF)-α-induced protein 3 (TNFAIP3) gene (Bagchi et al., 2012)."
Infections activates TNFAIP3.
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2
sparser
"Previous studies demonstrated that the polyubiquitination of Casp8 induced by Apo2L/TRAIL can be attenuated by A20. xref A20 also stably interacts with Casp8 in human T cell leukemia virus type I (HTLV‐I)–infected cells, thereby protecting them from apoptosis. xref We determined that Casp8 increased A20 expression by activating NF‐kappaB and cleaving RIP1."
sparser
"Conserved domain analysis revealed that two PtSAPs (-14 and -17) included one AN1 domain (AN1); PtSAP3 contained one A20 domain (A20); PtSAP13 contained two AN1 domains (AN1–AN1); PtSAP8 contained two AN1 domain, and two CH2–CH2 domains (AN1–AN1–CH2–CH2); and the remaining 14 SAP members included one A20 domain and one AN1 domain (A20–AN1) ( xref , xref and xref )."
sparser
"When we compared the expression patterns of A20-AN1 and AN1 castor bean SAP genes, we found that SAP genes of the same type did not exhibit similar expression patterns, suggesting that transcriptional regulation of castor bean SAP genes of the same type might vary in response to stresses."
sparser
"The 14–3–3 proteins also interact with A20 and may modulate the localization of A20 via chaperone activity. xref , xref However, 14–3–3 does not appear to regulate NF-κB suggesting that binding to A20 is for a distinct purpose. xref YMER (also known as CCDC50) was also reported to interact with A20, inhibit NF-κB and interact with ubiquitin via a ubiquitin-binding domain. xref However, YMER-deficient mice will be needed to firmly establish its role as an A20 and NF-κB regulator."
IFGFR1 affects TNFAIP3
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7
Benzo[a]pyrene affects TNFAIP3
7
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Benzo[a]pyrene increases the amount of TNFAIP3.
4
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Benzo[a]pyrene decreases the amount of TNFAIP3.
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sparser
"Nonetheless, depletion of TRIP6 can significantly enhance the association of A20 or CYLD with TRAF6 in ovarian cancer cells and promote the binding of A20 to TRAF6 in glioblastoma cells, suggesting that targeting TRIP6 may prove to be an effective strategy to restore the function of A20 and CYLD in restricting the NF-κB activity in these cancer cells."
sparser
"Nonetheless, depletion of TRIP6 by either shRNA ( xref ) or Cas9/sgRNA ( xref ) not only enhanced the association of TRAF6 with A20, but also with CYLD in untreated and treated cells, suggesting a significant role for TRIP6 in antagonizing the binding of TRAF6 to both A20 and CYLD in ovarian cancer cells."
sparser
"In this regard, here we provide evidence that the adaptor protein TRIP6 (thyroid hormone receptor-interacting protein 6), a specific interacting protein of the LPA2 receptor but not other LPA receptors, recruits TRAF6 to the LPA2 receptor and enhances the E3 ligase activity of TRAF6 by antagonizing the association of A20 and CYLD to TRAF6."
TNFAIP3 affects pathway
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7
sparser
"The 14–3–3 proteins also interact with A20 and may modulate the localization of A20 via chaperone activity. xref , xref However, 14–3–3 does not appear to regulate NF-κB suggesting that binding to A20 is for a distinct purpose. xref YMER (also known as CCDC50) was also reported to interact with A20, inhibit NF-κB and interact with ubiquitin via a ubiquitin-binding domain. xref However, YMER-deficient mice will be needed to firmly establish its role as an A20 and NF-κB regulator."
TNFAIP3 affects migration
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6
1
sparser
"Mothes et al. [155] used a modular modeling approach to determine the impact of different A20 feedback implementations on the dynamics of NF-κB. The authors used three different models (Lipniacki et al. [153] , Ashall et al. [146] , and Murakawa et al. [156] ), which had different A20 implementations against IKK inhibition, and combined them with a common IκBα-A20 negative feedback core module."
reach
"Furthermore, we observed a downregulation of several TNF-induced genes that play a central role in curtailing TNF signalling, including the inhibitors of NFkB, NFKBIZ and NFKBIA, RGS1, TNFAIP3 and AREG.Consistent with this observation, Oncostatin M (OSM), a pro-inflammatory cytokine shown to be increased in inflammatory bowel disease patients with poor response to anti-TNF therapy 27 , was also downregulated by iLD-IL-2."
| DOI
eidos
"A20 can block IL-17 production by interrupting the MAPK signaling pathway through abrogating K63 ubiquitination of TNF receptor associated factor 6 ( TRAF6 ) and preventing the prolonged phosphorylation of c-Jun-N-terminal-kinase ( JNK ) , which are both important for MAPK activation [ 46 ] ."
| PMC
reach
"Together, these data suggest that TNFα signaling via TNFR2 promotes the expression of the anti-inflammatory mediator TNFAIP3/A20, which seems to prevent IL-17A expression in regulatory T cells, as ablation of TNFα signaling suppresses TNFAIP3/A20 and results in increased IL-17A expression in human Treg."
sparser
"At this time, very little information is available regarding the interaction of TNFAIP3 and STAT3 activation, and what is there appears disease/tissue dependent: in liver, TNFAIP3 activity results in increased STAT3 phosphorylation and IL-6 induction via inhibition of suppressor of cytokine signaling 3 ( xref )."
sparser
"Conspicuously, 13 of the 1715 upregulated proteins and 3 of the 264 downregulated proteins were enlisted in A20-interacted proteins ( xref ; xref ), among which prohibitin (PHB) had been previously reported as a regulator of STAT3 phosphorylation. xref Afterwards, we performed co-IP assay by precipitating STAT3, A20 and PHB in cell lysate respectively, and confirmed that PHB directly interacted with A20 and STAT3 ( xref )."
sparser
"Mothes et al. [155] used a modular modeling approach to determine the impact of different A20 feedback implementations on the dynamics of NF-κB. The authors used three different models (Lipniacki et al. [153] , Ashall et al. [146] , and Murakawa et al. [156] ), which had different A20 implementations against IKK inhibition, and combined them with a common IκBα-A20 negative feedback core module."
sparser
"In contrast, RNF11 silencing did not result in increased expression of immune genes, apoptosis, or HRSV growth, indicating that this protein does not collaborate with A20 in the regulation of these processes, despite the fact that RNF11 seems to form a complex with A20, TAX1BP1, and ITCH to inhibit TNF and LPS-induced NF-κB signaling [ xref ]."
sparser
"Nonetheless, depletion of TRIP6 can significantly enhance the association of A20 or CYLD with TRAF6 in ovarian cancer cells and promote the binding of A20 to TRAF6 in glioblastoma cells, suggesting that targeting TRIP6 may prove to be an effective strategy to restore the function of A20 and CYLD in restricting the NF-κB activity in these cancer cells."
sparser
"Nonetheless, depletion of TRIP6 by either shRNA ( xref ) or Cas9/sgRNA ( xref ) not only enhanced the association of TRAF6 with A20, but also with CYLD in untreated and treated cells, suggesting a significant role for TRIP6 in antagonizing the binding of TRAF6 to both A20 and CYLD in ovarian cancer cells."
sparser
"In this regard, here we provide evidence that the adaptor protein TRIP6 (thyroid hormone receptor-interacting protein 6), a specific interacting protein of the LPA2 receptor but not other LPA receptors, recruits TRAF6 to the LPA2 receptor and enhances the E3 ligase activity of TRAF6 by antagonizing the association of A20 and CYLD to TRAF6."
Silicon dioxide affects TNFAIP3
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Silicon dioxide increases the amount of TNFAIP3. 6 / 6
6
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sparser
"Wild-type mouse embryonic fibroblasts (MEFs) or MEFs that lack expression of A20 ( A20 −/− ) or TAX1BP1 ( Tax1bp1 −/− ) were treated with IL-1 for various times, and the interactions between TRAF6, A20, and TAX1BP1 were monitored by immunoprecipitations and protein immunoblotting ( xref and xref )."
TNFAIP3 affects production
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6
sparser
"For examples, A20 negatively regulates RIG-I activity, NLRX1 interacts with MAVS and inhibits MAVS-mediated IFN production, RNF5 works as a ubiquitin E3 ligase to promote MITA degradation, IRAK-M impairs TLR signaling by blocking the formation of IRAK-TRAF6 complex, and ATF4 links integrated cellular stress responses and innate immune responses to down-regulate IRF7 and IFN expressions ( xref - xref )."
TNFAIP3 affects osteoclastogenesis
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6
TNFAIP3 affects lipopolysaccharide
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1
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TNFAIP3 inhibits lipopolysaccharide.
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1
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TNFAIP3 activates lipopolysaccharide.
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TNFAIP3 ubiquitinates TNFAIP3.
1
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1
"Full-length A20 protein wild-type (WT), the single point mutants Y614A or L626R or F615A, and the double mutants Y614A, L626R and Y614A, F615A were expressed in 293T cells and assayed with UbcH7 for the ability to auto-ubiquitinate A20. Only A20 with an intact Ub-binding site II on A20 ZnF4 was able to promote effective auto-ubiquitination."
TNFAIP3 inhibits TNFAIP3.
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TNFAIP3 decreases the amount of TNFAIP3.
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2
sparser
"The fact that MALT-1 ubiquitination by TRAF6 is essential for TCR- and BCR-induced activation of NF-κB and evidence that MALT-1 plays an important role in the pathogenesis of several autoimmune diseases (e.g., Multiple Sclerosis; Brüstle et al., xref ; Mc Guire et al., xref ) and lymphomas (e.g., Marginal B zone lymphoma and ABC-DLBCL; Ngo et al., xref ; Vega et al., xref ) suggest that MALT-1 inhibition by A20 plays an important role in the prevention of autoimmunity and lymphomas (Figure xref )."
sparser
"To demonstrate the generality of this approach to gene silencing, we used TLR9-positive mouse A20 B cell lymphoma cells to test CpG-siRNA internalization (Supplementary Fig. 6a), and gene silencing, for which we tested a chimeric conjugate linking CpG1668 ODN with a Dicer substrate siRNA specific for firefly luciferase (Luc) in inhibiting luciferase activity in A20-Luc cells (Supplementary Fig. 6 b)."
TNFAIP3 affects HA20
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6
sparser
"Previous studies demonstrated that the polyubiquitination of Casp8 induced by Apo2L/TRAIL can be attenuated by A20. xref A20 also stably interacts with Casp8 in human T cell leukemia virus type I (HTLV‐I)–infected cells, thereby protecting them from apoptosis. xref We determined that Casp8 increased A20 expression by activating NF‐kappaB and cleaving RIP1."
sparser
"These A20-Atg16l1 ΔIEC mice develop spontaneous IBD-like pathology characterized by severe inflammation in both small and large intestine, crypt abscesses with marked epithelial cell death, Paneth cell loss, and villi erosion, in contrast to single A20 ΔIEC or Atg16l1 ΔIEC mice, which do not develop overt intestinal abnormalities nor inflammation in homeostatic conditions."
sparser
"Both apoptosis and necroptosis have been associated with IBD xref , and although apoptotic death is considered less inflammatory due to the containment of the cell content within apoptotic bodies, we believe that in our A20-Atg16l1 dKO model apoptosis of the intestinal epithelial cells is the driving cell death mode triggering chronic intestinal inflammation, given the clear observation of cleaved caspase-3 positive cells in dKO mice."
sparser
"Wild-type mouse embryonic fibroblasts (MEFs) or MEFs that lack expression of A20 ( A20 −/− ) or TAX1BP1 ( Tax1bp1 −/− ) were treated with IL-1 for various times, and the interactions between TRAF6, A20, and TAX1BP1 were monitored by immunoprecipitations and protein immunoblotting ( xref and xref )."
eidos
"Mechanistic studies revealed that RNF31 was able to degrade A20 , which affected the inflammatory response and hepatocyte apoptosis mediated by the toll like receptor 4 ( TLR4 ) / myeloid differentiation factor88 ( MyD88 ) / nuclear transcription factor-kappaB ( NF-kappaB ) signaling pathway ."
sparser
"Enforced expression of NEMO in cells revealed that NEMO can both promote and block NF-kappaB activation and dramatically augments the phosphorylation of c-Jun. The findings suggest that the signaling activities of the IKK signalosome are regulated through binding of NEMO to RIP and A20 within the p55 TNF receptor complex."
Particulate Matter affects TNFAIP3
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Particulate Matter increases the amount of TNFAIP3. 6 / 6
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sparser
"To demonstrate the generality of this approach to gene silencing, we used TLR9-positive mouse A20 B cell lymphoma cells to test CpG-siRNA internalization (Supplementary Fig. 6a), and gene silencing, for which we tested a chimeric conjugate linking CpG1668 ODN with a Dicer substrate siRNA specific for firefly luciferase (Luc) in inhibiting luciferase activity in A20-Luc cells (Supplementary Fig. 6 b)."
sparser
"Enforced expression of NEMO in cells revealed that NEMO can both promote and block NF-kappaB activation and dramatically augments the phosphorylation of c-Jun. The findings suggest that the signaling activities of the IKK signalosome are regulated through binding of NEMO to RIP and A20 within the p55 TNF receptor complex."
sparser
"These A20-Atg16l1 ΔIEC mice develop spontaneous IBD-like pathology characterized by severe inflammation in both small and large intestine, crypt abscesses with marked epithelial cell death, Paneth cell loss, and villi erosion, in contrast to single A20 ΔIEC or Atg16l1 ΔIEC mice, which do not develop overt intestinal abnormalities nor inflammation in homeostatic conditions."
sparser
"Both apoptosis and necroptosis have been associated with IBD xref , and although apoptotic death is considered less inflammatory due to the containment of the cell content within apoptotic bodies, we believe that in our A20-Atg16l1 dKO model apoptosis of the intestinal epithelial cells is the driving cell death mode triggering chronic intestinal inflammation, given the clear observation of cleaved caspase-3 positive cells in dKO mice."
MiR-19b-3p affects TNFAIP3
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2
3
eidos
"Tumor necrosis factor-alpha-induced protein 3 ( TNFAIP3 ) , which has the function of the ubiquitin-editing enzyme , can inhibit the upstream signal transduction of the NF-kappaB signal pathway.117 Relative studies have shown that miR-19b-3p and miR-125b can directly suppress TNFAIP3 expression , thereby activating the NF-kappaB signal pathway , promote the proliferation of NPC cells , and inhibit the apoptosis of NPC cells.118 ,119 Ras-like estrogen-regulated growth inhibitor ( RERG ) is regarded as a potential tumor suppressor gene , expressed in a variety of normal tissues.120 ,121 Zhao et al. found that RERG was silenced by DNA hypermethylation in NPC cells ."
MiR-125b affects TNFAIP3
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4
MiR-125b inhibits TNFAIP3.
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1
2
eidos
"Tumor necrosis factor-alpha-induced protein 3 ( TNFAIP3 ) , which has the function of the ubiquitin-editing enzyme , can inhibit the upstream signal transduction of the NF-kappaB signal pathway.117 Relative studies have shown that miR-19b-3p and miR-125b can directly suppress TNFAIP3 expression , thereby activating the NF-kappaB signal pathway , promote the proliferation of NPC cells , and inhibit the apoptosis of NPC cells.118 ,119 Ras-like estrogen-regulated growth inhibitor ( RERG ) is regarded as a potential tumor suppressor gene , expressed in a variety of normal tissues.120 ,121 Zhao et al. found that RERG was silenced by DNA hypermethylation in NPC cells ."
MiR-125b activates TNFAIP3.
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2
Cyclosporin A affects TNFAIP3
5
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Cyclosporin A increases the amount of TNFAIP3.
3
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Cyclosporin A decreases the amount of TNFAIP3.
2
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sparser
"The hLa mutant R32A/K34A/K37A, whose mutated amino acids map to neither the winged-helix face nor the UUU-3’OH recognition site, had no defect in binding either substrate, while the hLa F65A/N66A/E70A and E70A/K74A/K76A mutants, whose mutations map to the canonical winged-helix recognition helix of the La motif, showed slightly impaired binding to both U10 and A20, suggesting they may be misfolded (data not shown)."
TNFAIP3 affects pyroptosis
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TNFAIP3 inhibits pyroptosis. 5 / 5
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eidos
"A20 also has the ability to inhibit pyroptosis in a mechanism that is dependent on active Casp1 , thereby restoring the IL-1beta production process Therefore , in the TNF-alpha inflammatory pathway , which is upstream of the inflammatory response , A20 can target RIPK1 for proteasomal degradation , thus protecting cells from NF-kappaB activation and the subsequent production of pro-inflammatory factors ."
| PMC
eidos
"Apoptosis and pyroptosis of NP cells increased gradually treated with LPS for 12 h , 24 h , and 48 h. Differently , the level of mitophagy increased first and then decreased , and was the highest at LPS treatment for 12 h. Overexpression or knockdown of A20 in NP cells revealed that A20 attenuated the pyroptosis , apoptosis , and production of inflammatory cytokines of NP cells induced by LPS , while A20 sponsored mitophagy , reduced ROS production and collapse of mitochondrial membrane potential ( DeltaPsim ) ."
TNFAIP3 affects polyubiquitination
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5
TNFAIP3 affects interaction
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2
TNFAIP3 affects cell growth
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TNFAIP3 inhibits cell growth.
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TNFAIP3 activates cell growth.
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TNFAIP3 activates cell growth. 2 / 2
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reach
"These results suggest that the downstream molecular mechanisms responsible for mediating FGFR1 function are through coordinating multiple signaling pathways that govern cell proliferation, behavior and differentiation.Among the iFGFR1-upregulated genes, we further studied the role of TNFAIP3 in FGFR1 signaling-promoted DCIS.COM cell growth."
TNFAIP3 affects activities
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TNFAIP3 affects activation NF-kappaB signaling pathway
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5
eidos
"RT-qPCR and Western blot analysis show that A20 inhibits activation of NF-kappaB signaling pathway in hepatocytes of ALF rats ( A ) mRNA expressions of A20 , NF-kappaB , TRAF6 , and RIP1 in hepatocytes after transfection detected by RT-qPCR ; ( B ) protein levels of A20 , NF-kappaB , TRAF6 , and RIP1 in hepatocytes after transfection detected by Western blot analysis ; ( C ) protein band patterns of A20 , NF-kappaB , TRAF6 , and RIP1 in hepatocytes after transfection detected by Western blot analysis ; * P < 0.05 , compared with the control group ; #P < 0.05 , compared with the blank and NC groups ; measurement data were expressed as mean + / - standard deviation ; the data were assessed by t-test ."
sparser
"The hLa mutant R32A/K34A/K37A, whose mutated amino acids map to neither the winged-helix face nor the UUU-3’OH recognition site, had no defect in binding either substrate, while the hLa F65A/N66A/E70A and E70A/K74A/K76A mutants, whose mutations map to the canonical winged-helix recognition helix of the La motif, showed slightly impaired binding to both U10 and A20, suggesting they may be misfolded (data not shown)."
sparser
"Moreover, the antisense LNA oligonucleotide, which was used to modulate A20 mRNA stability ( xref ) and hybridizes to the loop and the 3′part of the stem, reduced the binding of RC3H1-N2 to the 37-nucleotide A20 target sequence, suggesting that the specific blockade of both loop and stem pronouncedly reduced RC3H1 binding to A20 3′UTR ( xref )."
sparser
"For example, Walle et al. showed that the negative regulation of NLRP3 inflammasome activation induced by A20 markedly protects against the onset of RA-associated inflammation and cartilage destruction, highlighting the contribution of the NLRP3 inflammasome to the pathology of RA [ xref ]."
reach
"Using the MWCL-A20 and HBL-1-A20 , we were able to show that loss of TNFAIP3 enhances MYD88 -driven NF-κB and p38 signaling resulting in increased expression of NF-κB target genes IL-6 and CXCL10, known NF-κB target genes , have both been shown to be significantly upregulated in WM and DLBCL, and higher serum levels correlate with an inferior survival ."
reach
"Consistent with these observations, treatment of A20 deficient mice with broad-spectrum antibiotics rescues the severe inflammation and lethality, indicating that a dysregulated response to commensal intestinal flora is responsible for the constitutive TLR signaling in Tnfaip3 -/- mice [XREF_BIBR]."
sparser
"Moreover, the antisense LNA oligonucleotide, which was used to modulate A20 mRNA stability ( xref ) and hybridizes to the loop and the 3′part of the stem, reduced the binding of RC3H1-N2 to the 37-nucleotide A20 target sequence, suggesting that the specific blockade of both loop and stem pronouncedly reduced RC3H1 binding to A20 3′UTR ( xref )."
Polyubiquitin affects IKBKG
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4
Nickel sulfate affects TNFAIP3
4
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Carbon nanotube affects TNFAIP3
4
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sparser
"In vitro transcription-translation reactions of A20 and flag-tagged alleles of D4 indicate that the interaction between A20 and UDG is preserved in vitro, and furthermore, mutational inactivation of UDG catalytic activity (D68N and H191L) ( xref , purple text, above the schematic of the D4 ORF) had no effect on this interaction ( xref )."
sparser
"Mutation of the catalytic cysteine residue 103 in the OTU domain also abrogates A20 binding with Ubc13 and UbcH5c. xref The crystal structure of the A20 OTU domain reveals that cysteine 103 resides within an alpha helix domain that contributes to ubiquitin binding. xref Therefore, both the OTU domain and ZnF4 may coordinate interactions with ubiquitin, E2 enzymes and adaptor molecules such as TAX1BP1."
sparser
"Although wild-type A20 interacted with endogenous Ubc13 and UbcH5c in cells stimulated with LPS or IL-1, both A20 C103A and A20 ZnF4 mutants were defective for binding to Ubc13 and UbcH5c ( xref ) and thus were unable to inhibit TRAF6 ubiquitination or promote Ubc13 degradation ( xref )."
sparser
"Currently, studies have shown that A20 binds to TRAF through its N-terminus, and binds to ABIN and IKK-γ via its C-terminus, thereby exerting its regulatory effects on the activity of nuclear factor κB and AP-1. xref On the one hand, A20 down-regulates their activity levels, while on the other it also disrupts their synergistic regulatory effects on inflammatory response, exhibited as downregulation of the expression of inflammatory mediators such as TNF-α, IL-1, IL-6, and IL-8 and the inhibition of TNF-α-induced apoptosis. xref This will ultimately limit inflammation in the body and protect the cells from damage."
TNFAIP3 affects ubiquitination
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TNFAIP3 affects signals
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4
TNFAIP3 affects signal transduction
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1
TNFAIP3 inhibits signal transduction. 4 / 4
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3
1
reach
"More importantly, tnfaip3 and tnip1 genes play key roles to regulate NF-κB signaling in psoriasis, and Ebosin can increase the expression of A20, a key player in the negative feedback regulation of NF-kappaB signaling encoded by tnfaip3, which has been reported to attenuate NF-κB signaling pathway by editing the ubiquitination of proximal signaling proteins including TRAF6, MALT1, RIPK1, NEMO, UBCH5C, etc (44)."
reach
"In more than half of ABC DLBCL cases, deletions or inactivating mutations in the TNFAIP3 (A20) tumor suppressor gene and genetic defects in some other protooncogenes and tumor suppressor genes that regulate the NF-κB signaling pathway were found to have activated this signaling pathway irregularly (Compagno et al., 2009)."
TNFAIP3 affects responses
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2
2
TNFAIP3 affects cell differentiation
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4
TNFAIP3 inhibits cell differentiation.
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2
TNFAIP3 activates cell differentiation.
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2
sparser
"In vitro transcription-translation reactions of A20 and flag-tagged alleles of D4 indicate that the interaction between A20 and UDG is preserved in vitro, and furthermore, mutational inactivation of UDG catalytic activity (D68N and H191L) ( xref , purple text, above the schematic of the D4 ORF) had no effect on this interaction ( xref )."
sparser
"Mutation of the catalytic cysteine residue 103 in the OTU domain also abrogates A20 binding with Ubc13 and UbcH5c. xref The crystal structure of the A20 OTU domain reveals that cysteine 103 resides within an alpha helix domain that contributes to ubiquitin binding. xref Therefore, both the OTU domain and ZnF4 may coordinate interactions with ubiquitin, E2 enzymes and adaptor molecules such as TAX1BP1."
sparser
"Although wild-type A20 interacted with endogenous Ubc13 and UbcH5c in cells stimulated with LPS or IL-1, both A20 C103A and A20 ZnF4 mutants were defective for binding to Ubc13 and UbcH5c ( xref ) and thus were unable to inhibit TRAF6 ubiquitination or promote Ubc13 degradation ( xref )."
sparser
"Currently, studies have shown that A20 binds to TRAF through its N-terminus, and binds to ABIN and IKK-γ via its C-terminus, thereby exerting its regulatory effects on the activity of nuclear factor κB and AP-1. xref On the one hand, A20 down-regulates their activity levels, while on the other it also disrupts their synergistic regulatory effects on inflammatory response, exhibited as downregulation of the expression of inflammatory mediators such as TNF-α, IL-1, IL-6, and IL-8 and the inhibition of TNF-α-induced apoptosis. xref This will ultimately limit inflammation in the body and protect the cells from damage."
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4
TNFAIP3 affects PFKL protein
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4
TNFAIP3 binds OLIG3 and Arthritis, Rheumatoid. 2 / 2
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2
sparser
"This association locus was first identified in a GWAS xref and has been subsequently confirmed in multiple Caucasian and Asian cohorts. xref – xref Specifically, a study of 3962 RA patients and 3531 healthy controls demonstrated strong association (OR = 1.2; 95% CI: 1.1–1.3; P = 2.6 × 10 6 ) with a variant (rs6920220) in an intergenic region of chromosome 6q23 region between oligodendrocyte linear transcription factor 3 ( OLIG3 ) and TNF-α-induced protein 3 ( TNFAIP3 ). xref The validity of this study has been confirmed by a recent meta-analysis of seven studies investigating the association of the TNFAIP3-OLIG3 region with RA, which indicated a strong association of the variant rs6920220 (OR = 1.2, 95% CI: 1.2–1.3; P = 7.9 × 10 −17 ). xref Since the TNFAIP3 gene acts as a negative regulator of the transcription factor nuclear factor-κB (NFκB) in response to TNF- and toll-like receptor activation, xref , xref it is an attractive RA susceptibility candidate gene."
reach
"The present study supports an association between HLA-DRB1 SE alleles, PTPN22, OLIG3 and TNFAIP3, STAT4 and TRAF1/C5 with susceptibility to autoantibody positive RA, but only the TRAF1/C5 locus was associated with disease severity in this cohort, although this would no longer remain significant after correction for multiple comparisons."
reach
"Patient macrophages are polarized toward pyroptosis and exhibit abnormal staining for inflammasome components.Heterozygous germline mutations in TNFAIP3 cause a Behçet's‐like disease, characterized by early‐onset systemic inflammation, arthralgia/arthritis, oral/genital ulcers, and ocular inflammation described in six unrelated families.154
TNFAIP3 encodes the NF‐κB regulatory protein A20 which is a potent inhibitor of the NF‐κB signaling pathway via its deubiquitinase activity."
sparser
"Wild-type mouse embryonic fibroblasts (MEFs) or MEFs that lack expression of A20 ( A20 −/− ) or TAX1BP1 ( Tax1bp1 −/− ) were treated with IL-1 for various times, and the interactions between TRAF6, A20, and TAX1BP1 were monitored by immunoprecipitations and protein immunoblotting ( xref and xref )."
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TNFAIP3 binds OLIG3 and Arthritis, Rheumatoid. 2 / 2
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2
sparser
"This association locus was first identified in a GWAS xref and has been subsequently confirmed in multiple Caucasian and Asian cohorts. xref – xref Specifically, a study of 3962 RA patients and 3531 healthy controls demonstrated strong association (OR = 1.2; 95% CI: 1.1–1.3; P = 2.6 × 10 6 ) with a variant (rs6920220) in an intergenic region of chromosome 6q23 region between oligodendrocyte linear transcription factor 3 ( OLIG3 ) and TNF-α-induced protein 3 ( TNFAIP3 ). xref The validity of this study has been confirmed by a recent meta-analysis of seven studies investigating the association of the TNFAIP3-OLIG3 region with RA, which indicated a strong association of the variant rs6920220 (OR = 1.2, 95% CI: 1.2–1.3; P = 7.9 × 10 −17 ). xref Since the TNFAIP3 gene acts as a negative regulator of the transcription factor nuclear factor-κB (NFκB) in response to TNF- and toll-like receptor activation, xref , xref it is an attractive RA susceptibility candidate gene."
reach
"The present study supports an association between HLA-DRB1 SE alleles, PTPN22, OLIG3 and TNFAIP3, STAT4 and TRAF1/C5 with susceptibility to autoantibody positive RA, but only the TRAF1/C5 locus was associated with disease severity in this cohort, although this would no longer remain significant after correction for multiple comparisons."
reach
"XREF_BIBR Assessment of the underlying mechanism revealed that MTX triggered TNFAIP3 induction in GM-MO was significantly diminished (40%) after TS silencing with two different small interfering RNA (XREF_FIG), thus indicating that MTX triggered TNFAIP3 upregulation is partly dependent on TS expression."
IKBKG affects polyubiquitin
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4
(+)-JQ1 compound affects TNFAIP3
4
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Valproic acid affects TNFAIP3
3
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Trif affects TNFAIP3
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3
Protein phosphatase affects TNFAIP3
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3
3
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Circ-ATP5H affects TNFAIP3
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1
2
Bis(2-chloroethyl) sulfide affects TNFAIP3
3
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Bacterial infection affects TNFAIP3
3
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"Understanding the response of innate immune cells to pathogens may provide insights to host defenses and the tactics used by pathogens to circumvent these defenses. We used DNA microarrays to explore the responses of human macrophages to a variety of bacteria. Macrophages responded to a broad range of bacteria with a robust, shared pattern of gene expression. The shared response includes genes encoding receptors, signal transduction molecules, and transcription factors. This shared activation program transforms the macrophage into a cell primed to interact with its environment and to mount an immune response. Further study revealed that the activation program is induced by bacterial components that are Toll-like receptor agonists, including lipopolysaccharide, lipoteichoic acid, muramyl dipeptide, and heat shock proteins. Pathogen-specific responses were also apparent in the macrophage expression profiles. Analysis of Mycobacterium tuberculosis-specific responses revealed inhibition of interleukin-12 production, suggesting one means by which this organism survives host defenses. These results improve our understanding of macrophage defenses, provide insights into mechanisms of pathogenesis, and suggest targets for therapeutic intervention."
Aflatoxin B1 affects TNFAIP3
3
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TNFAIP3 affects trif
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3
TNFAIP3 affects protein phosphatase
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TNFAIP3 affects phosphorylation
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3
TNFAIP3 affects interactions
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2
1
TNFAIP3 affects induction
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3
TNFAIP3 affects growth
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3
TNFAIP3 affects glycolytic process
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3
TNFAIP3 affects effects
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3
reach
"The present study supports an association between HLA-DRB1 SE alleles, PTPN22, OLIG3 and TNFAIP3, STAT4 and TRAF1/C5 with susceptibility to autoantibody positive RA, but only the TRAF1/C5 locus was associated with disease severity in this cohort, although this would no longer remain significant after correction for multiple comparisons."
reach
"In contrast, IL-1 strongly stimulated the recruitment of p65 to 5 of the 8 genomic regions that contained genes shown to be regulated at the mRNA and transcriptional level by both HCoV-229E and IL-1 (see above and Fig 5D) whereas, for HCoV-229E-infected cells, only a moderate increase of p65 binding to the CXCL2, CXCL1, TNFAIP3 and IL8 loci could be detected (Fig 5D)."
reach
"After verifying that SFE could increase the content of p65 bound to IkappaBalpha and inhibit p65 from entering the nuclear to inactivate the NFkappaB pathway (XREF_FIG D, Supplementary Figure S7B), we further identified the inhibitory effect of SFE on p65 binding to TNFAIP3 and PLAU, which can be reversed by LPS treatment, analyzed by ChIP-PCR and luciferase reporter assays (XREF_FIG E, Supplementary Figure S8A)."
TNFAIP3 affects Neoplasm Metastasis
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TNFAIP3 activates Neoplasm Metastasis. 3 / 3
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2
1
reach
"However, when overexpressing TNFAIP3 and PLAU or upon activation of the NFkappaB pathway, all the inhibitory effects of SFE were reversed (XREF_FIG A-D), suggesting that SFE blocked the p65 promotion of TNFAIP3 and PLAU expression to inhibit ESCC cell proliferation and metastasis."
TNFAIP3 affects Cell Survival
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TNFAIP3 activates Cell Survival. 3 / 3
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2
reach
"Activation of canonical NF-κB in response to EGFR oncogene inhibition in mutant EGFR-bearing human and mouse lung cancer cells, drives tumour cell survival and residual disease in lung cancer via several established regulators of canonical NF-κB signalling and cell survival such as TNFAIP3 (TNFα-induced protein 3), BIRC3 (c-IAP2, TNFR2-TRAF signalling complex protein) and IL-6 [16]."
sparser
"A case of advanced lung adenocarcinoma with rare COX7A2L-ALK (C2:A20) fusion detected by NGS was reported in Peking Union Medical College Hospital, and all cases with rare ALK fusion mutations were searched from medical datebase from January 1, 2014 to March 31, 2021, to investigate the treatment of rare ALK fusion mutations with ALK inhibitors."
eidos
"Additionally , domain-specific mutant mice can be generated by mutating OTU ( C103A ) , ZnF4 ( C609A and C612A ) , or ZnF7 ( C764A and C767A ) and other specific sites The inflammatory features of arthritis and the anti-inflammatory function of A20 suggest that A20 can suppress arthritis by restricting inflammation , which has been verified by a growing number of studies ."
| PMC
eidos
"A20 prevents arthritis by inhibiting macrophage necroptosis and restricting spontaneous immune activation through its ZnF7 Necroptosis is a modified form of necrosis in which dead cells break up and release intracellular components , triggering an innate immune response that includes IL-1beta release and NLRP3 inflammasome activation [ 29 , 57 ] ."
| PMC
TNFAIP3 affects Activation
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3
reach
"The present study supports an association between HLA-DRB1 SE alleles, PTPN22, OLIG3 and TNFAIP3, STAT4 and TRAF1/C5 with susceptibility to autoantibody positive RA, but only the TRAF1/C5 locus was associated with disease severity in this cohort, although this would no longer remain significant after correction for multiple comparisons."
reach
"We further show that activation of NF-kappaB by OPN occurs through a unique mechanism in which intracellular OPN (iOPN) causes transcriptional downregulation of the NF-kappaB inhibitors, A20 and TNFAIP3 and ABIN1 and TNIP1, and secretory OPN (sOPN) promotes receptor mediated activation of NF-kappaB."
SKBHT affects TNFAIP3
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2
1
PPP2 affects protein phosphatase
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3
Let-7 miRNAs affects TNFAIP3
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3
sparser
"DUB-E3 interactions are used for mutual ubiquitin-dependent regulation (e.g., to control each other’s stability, see above) or for editing ubiquitin chain architecture on particular substrates (as shown for the hybrid DUB/E3 enzyme A20 and CYLD-ITCH complexes during inflammatory signaling [ xref , xref ])."
HAND2-AS1 affects TNFAIP3
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3
CYLD affects protein phosphatase
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3
sparser
"DUB-E3 interactions are used for mutual ubiquitin-dependent regulation (e.g., to control each other’s stability, see above) or for editing ubiquitin chain architecture on particular substrates (as shown for the hybrid DUB/E3 enzyme A20 and CYLD-ITCH complexes during inflammatory signaling [ xref , xref ])."
sparser
"A case of advanced lung adenocarcinoma with rare COX7A2L-ALK (C2:A20) fusion detected by NGS was reported in Peking Union Medical College Hospital, and all cases with rare ALK fusion mutations were searched from medical datebase from January 1, 2014 to March 31, 2021, to investigate the treatment of rare ALK fusion mutations with ALK inhibitors."
C14-Tri-LAN-Gly affects TNFAIP3
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3
Tryptophol acetate affects TNFAIP3
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2
Trovafloxacin affects TNFAIP3
2
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Titanium dioxide affects TNFAIP3
2
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Tetrachloromethane affects TNFAIP3
2
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Sodium dodecyl sulfate affects TNFAIP3
2
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Small interfering RNA affects TNFAIP3
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2
Resveratrol affects TNFAIP3
2
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Reactive oxygen species affects TNFAIP3
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2
Precursor mRNA affects TNFAIP3
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2
Polyubiquitin chains affects TNFAIP3
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2
PlTIM affects TNFAIP3
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2
Phenethyl isothiocyanate affects TNFAIP3
2
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P65 affects TNFAIP3
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2
MiR-125a affects TNFAIP3
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2
Messenger RNA affects TNFAIP3
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2
Measles virus P protein affects TNFAIP3
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2
Magnetite nanoparticle affects TNFAIP3
2
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sparser
"Using a reductionist 3-cell system comprising GFP-specific (JEDI) CD8 T cells ( xref , xref ), Ag + A20-GFP cells, and Ag − A20-mCherry cells ( xref ), we exerted strong iterative Ag-specific T cell selection pressure on the GFP + population ( xref ) and sequenced surviving cells to measure changes in the frequency of targeted genes ( xref )."
Hsa-miR-19b-3p affects TNFAIP3
2
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Hsa-miR-19a-3p affects TNFAIP3
2
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Hsa-miR-125b-5p affects TNFAIP3
2
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Hsa-miR-125a-5p affects TNFAIP3
2
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Diarsenic trioxide affects TNFAIP3
2
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Cylindrospermopsin zwitterion affects TNFAIP3
2
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Crocidolite asbestos affects TNFAIP3
2
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Complex I affects TNFAIP3
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2
Capsid protein affects TNFAIP3
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2
Cadmium atom affects TNFAIP3
2
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Anti-IL6 receptor biologic tocilizumab affects TNFAIP3
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2
All-trans-retinoic acid affects TNFAIP3
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2
Activating USF1 affects TNFAIP3
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2
eidos
"We also showed previously that in the human promyelocytic leukemia cell line ( HL-60 ) , which differentiates to the monocyte and macrophage phenotype in response to PMA , zinc upregulates the expression of A20 and the binding of A20 transactivating factor to DNA , which results in the inhibition of NF-kB activation ( 44 , 45 ) ."
eidos
"We have also shown previously that in the promyelocytic leukemia cell line HL-60 , which differentiates to a monocyte and macrophage phenotype in response to phorbol-12-myristate-13-acetate PHA , zinc upregulated the expression of A20 , and the binding of A20 transactivating factor to DNA , which resulted in the inhibition of NF-kappaB activation ( Bao et al ., 2010 ; Prasad et al ., 1993 Prasad et al ., , 2007 ."
| PMC
Virus Diseases affects TNFAIP3
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2
Ubiquitin affects E3_Ub_ligase
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2
sparser
"cDNAs encoding Myc-tagged forms of USP4, USP11, Ataxin-3 and A20 were gifts from Dr P.J. Lehner (University of Cambridge, UK) (51), Dr J. Yang (Baylor College of Medicine, Houston, USA) (52), Dr E.A. Fon (Montreal Neurological Institute, Canada) (23) and Dr K. Li (University of Texas Medical Branch, Galveston, USA) (53), respectively."
sparser
"Mutation of the catalytic cysteine residue 103 in the OTU domain also abrogates A20 binding with Ubc13 and UbcH5c. xref The crystal structure of the A20 OTU domain reveals that cysteine 103 resides within an alpha helix domain that contributes to ubiquitin binding. xref Therefore, both the OTU domain and ZnF4 may coordinate interactions with ubiquitin, E2 enzymes and adaptor molecules such as TAX1BP1."
sparser
"Although wild-type A20 interacted with endogenous Ubc13 and UbcH5c in cells stimulated with LPS or IL-1, both A20 C103A and A20 ZnF4 mutants were defective for binding to Ubc13 and UbcH5c ( xref ) and thus were unable to inhibit TRAF6 ubiquitination or promote Ubc13 degradation ( xref )."
sparser
"Mutation of the catalytic cysteine residue 103 in the OTU domain also abrogates A20 binding with Ubc13 and UbcH5c. xref The crystal structure of the A20 OTU domain reveals that cysteine 103 resides within an alpha helix domain that contributes to ubiquitin binding. xref Therefore, both the OTU domain and ZnF4 may coordinate interactions with ubiquitin, E2 enzymes and adaptor molecules such as TAX1BP1."
sparser
"Although wild-type A20 interacted with endogenous Ubc13 and UbcH5c in cells stimulated with LPS or IL-1, both A20 C103A and A20 ZnF4 mutants were defective for binding to Ubc13 and UbcH5c ( xref ) and thus were unable to inhibit TRAF6 ubiquitination or promote Ubc13 degradation ( xref )."
Tobacco Smoke Pollution affects TNFAIP3
2
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TRAF1 affects Arthritis, Rheumatoid
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2
TNFAIP3 affects ubiquitination degradation PFKL
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2
TNFAIP3 affects translocation
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2
TNFAIP3 affects transcription, DNA-templated
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2
TNFAIP3 affects transactivation
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TNFAIP3 affects signalling
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2
TNFAIP3 affects signal
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TNFAIP3 affects set inflammatory
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2
eidos
"With 24 hour IL-17A simulation , a large set of inflammatory genes were repressed by both A20 or ABIN1 overexpression : DEFB4A , C3 , S100A7 , CXCL8 , SAA2 , CXCL5 , CSF2 , IL36G , SAA1 , CXCL1 , CXCL6 , IL24 , IL74 , CXCL3 , S100A8 , andCXCL22 , although generally to a greater extent by A20 ."
TNFAIP3 affects response
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2
TNFAIP3 affects release
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2
TNFAIP3 affects programmed cell death
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2
TNFAIP3 affects pro-inflammatory cytokine
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2
eidos
"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 ] ."
TNFAIP3 affects polyubiquitin chains
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2
TNFAIP3 affects plTIM
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2
TNFAIP3 affects periodontal bone resorption
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2
TNFAIP3 affects p65
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2
TNFAIP3 affects osteoclast differentiation
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2
TNFAIP3 affects mutations
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2
TNFAIP3 affects motility
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2
TNFAIP3 affects morphine-induced macrophage apoptosis
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2
TNFAIP3 affects maturation pro-IL-1beta
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2
sparser
"Using a reductionist 3-cell system comprising GFP-specific (JEDI) CD8 T cells ( xref , xref ), Ag + A20-GFP cells, and Ag − A20-mCherry cells ( xref ), we exerted strong iterative Ag-specific T cell selection pressure on the GFP + population ( xref ) and sequenced surviving cells to measure changes in the frequency of targeted genes ( xref )."
TNFAIP3 affects innate immune response
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1
1
TNFAIP3 affects inflammatory response M1 polarization macrophages
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2
TNFAIP3 affects immune response
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2
TNFAIP3 affects human diseases
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2
TNFAIP3 affects hepatocytes rats
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2
eidos
"CCK-8 assay shows that A20 promotes the proliferation of hepatocytes in ALF rats * P < 0.05 , compared with the control group ; #P < 0.05 , compared with the blank and NC groups ; measurement data were expressed as mean + / - standard deviation ; the data at different time points were assessed by repeated-measures analysis of variance ."
TNFAIP3 affects function
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2
TNFAIP3 affects effect
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2
TNFAIP3 affects de-ubiquitination RIP1
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2
TNFAIP3 affects daphnetin
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2
TNFAIP3 affects complex I
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2
TNFAIP3 affects cell glycolysis
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2
TNFAIP3 affects cell cycle
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2
TNFAIP3 activates cell cycle. 2 / 2
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2
eidos
"Flow cytometry shows that A20 promotes cell cycle progression and inhibits apoptosis of hepatocytes in ALF rats ( A ) Cell cycle entry in each group determined by PI staining of flow cytometry ; ( B ) cell proportion in different stages in each group ; ( C ) apoptosis of hepatocytes in each group detected by Annexin V-FITC / PI double staining of flow cytometry ; ( D ) apoptotic rate of rats in each group ; * P < 0.05 , compared with the control group ; #P < 0.05 , compared with the blank and NC groups ; measurement data were expressed as mean + / - standard deviation ; the data were assessed by one-way analysis of variance ."
TNFAIP3 affects cardiac fibrosis
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2
TNFAIP3 affects capsid protein
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2
TNFAIP3 affects basal eNOS
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2
TNFAIP3 affects autophagy dependent regulation TRAF6 ubiquitination
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2
TNFAIP3 affects arthritis development
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2
TNFAIP3 affects apoptosis hepatocytes
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2
TNFAIP3 affects angiogenesis
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2
TNFAIP3 affects allergic asthma
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2
TNFAIP3 inhibits allergic asthma. 2 / 2
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2
TNFAIP3 affects airway epithelial cytokine
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2
TNFAIP3 affects Wnt/β-catenin
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2
sparser
"cDNAs encoding Myc-tagged forms of USP4, USP11, Ataxin-3 and A20 were gifts from Dr P.J. Lehner (University of Cambridge, UK) (51), Dr J. Yang (Baylor College of Medicine, Houston, USA) (52), Dr E.A. Fon (Montreal Neurological Institute, Canada) (23) and Dr K. Li (University of Texas Medical Branch, Galveston, USA) (53), respectively."
sparser
"Mutation of the catalytic cysteine residue 103 in the OTU domain also abrogates A20 binding with Ubc13 and UbcH5c. xref The crystal structure of the A20 OTU domain reveals that cysteine 103 resides within an alpha helix domain that contributes to ubiquitin binding. xref Therefore, both the OTU domain and ZnF4 may coordinate interactions with ubiquitin, E2 enzymes and adaptor molecules such as TAX1BP1."
sparser
"Although wild-type A20 interacted with endogenous Ubc13 and UbcH5c in cells stimulated with LPS or IL-1, both A20 C103A and A20 ZnF4 mutants were defective for binding to Ubc13 and UbcH5c ( xref ) and thus were unable to inhibit TRAF6 ubiquitination or promote Ubc13 degradation ( xref )."
TNFAIP3 affects TNF-mediated apoptosis
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2
TNFAIP3 affects TNF-induced apoptosis
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2
sparser
"A4 was then treated with a cocktail of TFA/TIPS/H 2 O at 45 °C to remove the A20-Mob and yielded the corresponding A20-thiol product A5 in 60% yield for two steps from purified A3 . xref Next, protected B chain [B7-Acm, B19-Trt] B1 was generated through Fmoc-SPPS and activated with DTDP during acidic cleavage to give the [B7- Acm, B19-SPy] chain B2 . xref "
TNFAIP3 affects Receptors, Antigen, B-Cell
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2
reach
"The present study supports an association between HLA-DRB1 SE alleles, PTPN22, OLIG3 and TNFAIP3, STAT4 and TRAF1/C5 with susceptibility to autoantibody positive RA, but only the TRAF1/C5 locus was associated with disease severity in this cohort, although this would no longer remain significant after correction for multiple comparisons."
sparser
"We searched publicly available ChIP-seq results associated with p65 and aligned the data to the GRCh38/hg38 reference assembly using UCSC Browser, finding that p65 can bind to the promoter regions of CXCL10 , TNFAIP3 , INHBA , and PLAU and the second intron region of TNFAIP3 in various kinds of cancer cells and samples."
sparser
"Conspicuously, 13 of the 1715 upregulated proteins and 3 of the 264 downregulated proteins were enlisted in A20-interacted proteins ( xref ; xref ), among which prohibitin (PHB) had been previously reported as a regulator of STAT3 phosphorylation. xref Afterwards, we performed co-IP assay by precipitating STAT3, A20 and PHB in cell lysate respectively, and confirmed that PHB directly interacted with A20 and STAT3 ( xref )."
TNFAIP3 affects P7C3
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2
sparser
"Moreover, a previous study demonstrated that the SFTSV NSs binds and inhibits A20-binding inhibitor of NF-κB 2 (ABIN2) to form complex with its interaction partners, tumor progression locus 2 (TPL2) and p105, resulted in the marked upregulation of anti-inflammatory cytokine IL-10 ( xref ) [ xref ]; p105/TPL2 complex regulates the expression of inflammatory genes, including anti-inflammatory gene IL10 , in which the signaling cascade is inhibited by ABIN2 binding to this complex."
sparser
"Several DUBs, including A20, CYLD and USP7, have been reported to downregulate NF- κ B. Co-IP assays were thus carried out to examine the interactions between these enzymes and HSCARG, and the results showed that HSCARG interacts weakly with A20 or CYLD but strongly interacts with USP7 ( xref , xref )."
TNFAIP3 affects NLRP3-mediated M1 macrophage polarization
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2
TNFAIP3 affects NF-kappaB-dependent gene
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2
TNFAIP3 affects NF-kappaB pathway
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2
sparser
"However, unexpectedly, the extent and duration of TNF-induced TRAF2 recruitment into complex I was not affected by A20 overexpression ( xref , second row), indicating that suppression of TNF-induced JNK activation by A20 is independent of TRAF2 recruitment into complex I. This conjecture also seems to be consistent with the earlier observation that A20 is capable of protecting TRAF2/5 DKO MEFs against TNF-induced cell death ( xref )."
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2
TNFAIP3 affects Inflammatory Bowel Disease
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2
sparser
"We searched publicly available ChIP-seq results associated with p65 and aligned the data to the GRCh38/hg38 reference assembly using UCSC Browser, finding that p65 can bind to the promoter regions of CXCL10 , TNFAIP3 , INHBA , and PLAU and the second intron region of TNFAIP3 in various kinds of cancer cells and samples."
TNFAIP3 affects HHV4_LMP-1
2
|
TNFAIP3 affects HAND2-AS1 overexpression RA-FLSs
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2
TNFAIP3 affects Dendritic Cells
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2
TNFAIP3 activates Dendritic Cells. 2 / 2
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2
reach
"20
,
21
Several models of DC‐specific deletion of TNFAIP3 in CD11c cells have shown that this molecule limits DC activation, and in the absence of TNFAIP3, DCs produce higher levels of cytokines, express higher co‐stimulatory molecules, resist to cell death, and activate auto‐reactive T‐ and B‐cell responses."
TNFAIP3 affects DRE-associated E-box domain
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2
TNFAIP3 affects Carcinogenesis
|
1
1
sparser
"We searched publicly available ChIP-seq results associated with p65 and aligned the data to the GRCh38/hg38 reference assembly using UCSC Browser, finding that p65 can bind to the promoter regions of CXCL10 , TNFAIP3 , INHBA , and PLAU and the second intron region of TNFAIP3 in various kinds of cancer cells and samples."
sparser
"cDNAs encoding Myc-tagged forms of USP4, USP11, Ataxin-3 and A20 were gifts from Dr P.J. Lehner (University of Cambridge, UK) (51), Dr J. Yang (Baylor College of Medicine, Houston, USA) (52), Dr E.A. Fon (Montreal Neurological Institute, Canada) (23) and Dr K. Li (University of Texas Medical Branch, Galveston, USA) (53), respectively."
sparser
"cDNAs encoding Myc-tagged forms of USP4, USP11, Ataxin-3 and A20 were gifts from Dr P.J. Lehner (University of Cambridge, UK) (51), Dr J. Yang (Baylor College of Medicine, Houston, USA) (52), Dr E.A. Fon (Montreal Neurological Institute, Canada) (23) and Dr K. Li (University of Texas Medical Branch, Galveston, USA) (53), respectively."
TBK1 affects IKK_complex
|
1
1
sparser
"Conspicuously, 13 of the 1715 upregulated proteins and 3 of the 264 downregulated proteins were enlisted in A20-interacted proteins ( xref ; xref ), among which prohibitin (PHB) had been previously reported as a regulator of STAT3 phosphorylation. xref Afterwards, we performed co-IP assay by precipitating STAT3, A20 and PHB in cell lysate respectively, and confirmed that PHB directly interacted with A20 and STAT3 ( xref )."
sparser
"A4 was then treated with a cocktail of TFA/TIPS/H 2 O at 45 °C to remove the A20-Mob and yielded the corresponding A20-thiol product A5 in 60% yield for two steps from purified A3 . xref Next, protected B chain [B7-Acm, B19-Trt] B1 was generated through Fmoc-SPPS and activated with DTDP during acidic cleavage to give the [B7- Acm, B19-SPy] chain B2 . xref "
RT-qPCR affects TNFAIP3
|
2
R-CHOP affects TNFAIP3
|
2
reach
"The present study supports an association between HLA-DRB1 SE alleles, PTPN22, OLIG3 and TNFAIP3, STAT4 and TRAF1/C5 with susceptibility to autoantibody positive RA, but only the TRAF1/C5 locus was associated with disease severity in this cohort, although this would no longer remain significant after correction for multiple comparisons."
sparser
"We searched publicly available ChIP-seq results associated with p65 and aligned the data to the GRCh38/hg38 reference assembly using UCSC Browser, finding that p65 can bind to the promoter regions of CXCL10 , TNFAIP3 , INHBA , and PLAU and the second intron region of TNFAIP3 in various kinds of cancer cells and samples."
sparser
"Conspicuously, 13 of the 1715 upregulated proteins and 3 of the 264 downregulated proteins were enlisted in A20-interacted proteins ( xref ; xref ), among which prohibitin (PHB) had been previously reported as a regulator of STAT3 phosphorylation. xref Afterwards, we performed co-IP assay by precipitating STAT3, A20 and PHB in cell lysate respectively, and confirmed that PHB directly interacted with A20 and STAT3 ( xref )."
P7C3 affects TNFAIP3
|
2
OLIG3 affects Arthritis, Rheumatoid
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2
TNFAIP3 binds OLIG3 and Arthritis, Rheumatoid. 2 / 2
|
2
sparser
"This association locus was first identified in a GWAS xref and has been subsequently confirmed in multiple Caucasian and Asian cohorts. xref – xref Specifically, a study of 3962 RA patients and 3531 healthy controls demonstrated strong association (OR = 1.2; 95% CI: 1.1–1.3; P = 2.6 × 10 6 ) with a variant (rs6920220) in an intergenic region of chromosome 6q23 region between oligodendrocyte linear transcription factor 3 ( OLIG3 ) and TNF-α-induced protein 3 ( TNFAIP3 ). xref The validity of this study has been confirmed by a recent meta-analysis of seven studies investigating the association of the TNFAIP3-OLIG3 region with RA, which indicated a strong association of the variant rs6920220 (OR = 1.2, 95% CI: 1.2–1.3; P = 7.9 × 10 −17 ). xref Since the TNFAIP3 gene acts as a negative regulator of the transcription factor nuclear factor-κB (NFκB) in response to TNF- and toll-like receptor activation, xref , xref it is an attractive RA susceptibility candidate gene."
sparser
"Moreover, a previous study demonstrated that the SFTSV NSs binds and inhibits A20-binding inhibitor of NF-κB 2 (ABIN2) to form complex with its interaction partners, tumor progression locus 2 (TPL2) and p105, resulted in the marked upregulation of anti-inflammatory cytokine IL-10 ( xref ) [ xref ]; p105/TPL2 complex regulates the expression of inflammatory genes, including anti-inflammatory gene IL10 , in which the signaling cascade is inhibited by ABIN2 binding to this complex."
NOD1 agonist affects TNFAIP3
|
2
sparser
"Several DUBs, including A20, CYLD and USP7, have been reported to downregulate NF- κ B. Co-IP assays were thus carried out to examine the interactions between these enzymes and HSCARG, and the results showed that HSCARG interacts weakly with A20 or CYLD but strongly interacts with USP7 ( xref , xref )."
sparser
"Moreover, a previous study demonstrated that the SFTSV NSs binds and inhibits A20-binding inhibitor of NF-κB 2 (ABIN2) to form complex with its interaction partners, tumor progression locus 2 (TPL2) and p105, resulted in the marked upregulation of anti-inflammatory cytokine IL-10 ( xref ) [ xref ]; p105/TPL2 complex regulates the expression of inflammatory genes, including anti-inflammatory gene IL10 , in which the signaling cascade is inhibited by ABIN2 binding to this complex."
reach
"In conclusion, these data indicate that mice harboring TNFAIP3‐deficient Langerin cDC1s especially displayed increased numbers of IFNγ‐producing CD8 T cells upon either a single HDM exposure or repetitive exposure with HDM.3.5
Blockade of IFNgamma restores eosinophilic airway inflammation in Tnfaip3
Lg-KO mice."
|
2
INPP5D affects plTIM
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2
sparser
"We searched publicly available ChIP-seq results associated with p65 and aligned the data to the GRCh38/hg38 reference assembly using UCSC Browser, finding that p65 can bind to the promoter regions of CXCL10 , TNFAIP3 , INHBA , and PLAU and the second intron region of TNFAIP3 in various kinds of cancer cells and samples."
IKK_complex affects TBK1, and TNFAIP3
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1
1
IKBKG affects polyubiquitin chains
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2
sparser
"Mechanistically, AKG exerted its anti-inflammatory effect by promoting the hydroxylation and degradation of HIF1A to reduce its Cd-induced overexpression in vivo and in vitro, avoiding the inhibition of the TNFAIP3 promoter by HIF1A. Moreover, the protective effect of AKG was significantly weaker in Cd-treated primary hepatocytes transfected with HIF1A pcDNA."
HHV4_LMP-1 affects TNFAIP3
2
|
HCoV-229E affects TNFAIP3
|
2
E3_Ub_ligase affects Ubiquitin
|
2
DRE-associated E-box domain affects USF1
|
2
sparser
"Several DUBs, including A20, CYLD and USP7, have been reported to downregulate NF- κ B. Co-IP assays were thus carried out to examine the interactions between these enzymes and HSCARG, and the results showed that HSCARG interacts weakly with A20 or CYLD but strongly interacts with USP7 ( xref , xref )."
sparser
"We searched publicly available ChIP-seq results associated with p65 and aligned the data to the GRCh38/hg38 reference assembly using UCSC Browser, finding that p65 can bind to the promoter regions of CXCL10 , TNFAIP3 , INHBA , and PLAU and the second intron region of TNFAIP3 in various kinds of cancer cells and samples."
sparser
"cDNAs encoding Myc-tagged forms of USP4, USP11, Ataxin-3 and A20 were gifts from Dr P.J. Lehner (University of Cambridge, UK) (51), Dr J. Yang (Baylor College of Medicine, Houston, USA) (52), Dr E.A. Fon (Montreal Neurological Institute, Canada) (23) and Dr K. Li (University of Texas Medical Branch, Galveston, USA) (53), respectively."
Arthritis, Rheumatoid affects TRAF1
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2
Arthritis, Rheumatoid affects OLIG3, and TNFAIP3
|
2
TNFAIP3 binds OLIG3 and Arthritis, Rheumatoid. 2 / 2
|
2
sparser
"This association locus was first identified in a GWAS xref and has been subsequently confirmed in multiple Caucasian and Asian cohorts. xref – xref Specifically, a study of 3962 RA patients and 3531 healthy controls demonstrated strong association (OR = 1.2; 95% CI: 1.1–1.3; P = 2.6 × 10 6 ) with a variant (rs6920220) in an intergenic region of chromosome 6q23 region between oligodendrocyte linear transcription factor 3 ( OLIG3 ) and TNF-α-induced protein 3 ( TNFAIP3 ). xref The validity of this study has been confirmed by a recent meta-analysis of seven studies investigating the association of the TNFAIP3-OLIG3 region with RA, which indicated a strong association of the variant rs6920220 (OR = 1.2, 95% CI: 1.2–1.3; P = 7.9 × 10 −17 ). xref Since the TNFAIP3 gene acts as a negative regulator of the transcription factor nuclear factor-κB (NFκB) in response to TNF- and toll-like receptor activation, xref , xref it is an attractive RA susceptibility candidate gene."
Arthritis, Rheumatoid affects Lupus Erythematosus, Systemic, and TNFAIP3
|
2
Air Pollutants affects TNFAIP3
2
|
sparser
"cDNAs encoding Myc-tagged forms of USP4, USP11, Ataxin-3 and A20 were gifts from Dr P.J. Lehner (University of Cambridge, UK) (51), Dr J. Yang (Baylor College of Medicine, Houston, USA) (52), Dr E.A. Fon (Montreal Neurological Institute, Canada) (23) and Dr K. Li (University of Texas Medical Branch, Galveston, USA) (53), respectively."
reach
"A systematic search for adiponectin inducible genes with established anti-inflammatory properties revealed that adiponectin augmented the expression of A20, suppressor of cytokine signaling (SOCS) 3, B-cell CLL and lymphoma (BCL) 3, TNF receptor associated factor (TRAF) 1, and TNFAIP3 interacting protein (TNIP) 3."
4-hydroxyphenyl retinamide affects TNFAIP3
1
|
1
4-hydroxyphenyl retinamide increases the amount of TNFAIP3. 2 / 2
1
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1
17beta-estradiol affects TNFAIP3
2
|