ライフサイエンスコーパス: TNFAIP3

1 mor necrosis factor-alpha-induced protein 3 (TNFAIP3).

2 r necrosis factor alpha-related protein A20 (TNFAIP3).

3 on by targeting TNF alpha-induced protein 3 (TNFAIP3).

4 ed genetic association between psoriasis and TNFAIP3.

5 luding rs5029937, located in the intron 2 of TNFAIP3.

6 identified psoriasis variants near IL23R and TNFAIP3.

7 cHL and PMBCL, with SOCS1 (45%), B2M (45%), TNFAIP3 (35%), GNA13 (35%), LRRN3 (32%), and NFKBIA (29%

8 he 15 trait/disease-associated haplotypes at TNFAIP3, 9 have at least one variant meeting one or both

9 Polymorphisms in A20 (TNFAIP3), a negative regulator of ubiquitin-mediated imm

10 d NF-kappaB that enhanced expression of A20 (TNFAIP3), a potent inhibitor of NF-kappaB.

11 A20 (TNFAIP3), a ubiquitin-editing enzyme, has emerged as one

12 s by directly binding the promoter region of Tnfaip3, a deubiquitinating enzyme in TLR signaling.

13 t least partially explained by repression of TNFAIP3, a negative regulator of NF-kappaB signaling.

14 s were activated by targeted deletion of A20/Tnfaip3, a negative regulator of NF-kappaB signaling.

15 ugh gain and loss-of-function studies of A20/TNFAIP3, a ubiquitous NF-kappaB inhibitor with establish

16 ion of anti-inflammatory TNF targets such as TNFAIP3 (A20) and NFKBIA was selectively spared or augme

17 In cancer cells, Tnfaip3 (A20) deletion activated the TNF-nuclear factor

18 Genetic TNFAIP3 (A20) inactivation is a classical somatic lympho

19 Ocular adnexal EMZL shows frequent TNFAIP3 (A20) mutation/deletion that significantly assoc

20 lymphoma (HL) cases display inactivation of TNFAIP3 (A20), a ubiquitin-editing protein that regulate

21 cancer (TNBC) cell lines via upregulation of TNFAIP3(A20).

22 matory molecule TNF-alpha-induced protein 3 (TNFAIP3)/A20 in memory CD4(+) T cells.

23 mor necrosis factor alpha-induced protein 3 (TNFAIP3, A20) gene, a negative regulator of NF-kappaB, w

24 reover, it provides novel targets related to TNFAIP3/A20 activity for superior therapeutic regimens i

25 Regulation of TNFAIP3/A20 expression and cognate IL-17A production in

26 We found an inverse relationship between TNFAIP3/A20 expression levels and IL-17A production.

27 evidence for an inverse relationship between TNFAIP3/A20 expression levels and IL-17A-producing T cel

28 und the archetypal negative immune regulator TNFAIP3/A20 in mice.

29 Inhibition of TNFAIP3/A20 promotes kinase activity of p38 mitogen-acti

30 mor necrosis factor alpha-induced protein-3 (TNFAIP3/A20) and impaired necroptotic cell death.

31 s effect to the ability of miR-29b to target TNFAIP3/A20, a negative regulator of NF-kappaB signaling

32 onstrate that the ubiquitin-modifying enzyme TNFAIP3/A20, an upstream regulator of T cell receptor (T

33 nts, including CCL5/RANTES, CXCL1/GRO-alpha, TNFAIP3/A20, and interleukin-6.

34 This puts TNFAIP3/A20, combined with IL-17A expression, on the map

35 Anti-TNF treatment interferes in the TNFAIP3/A20-mediated anti-inflammatory feedback loop in

36 A long noncoding RNA, LincRNA-Tnfaip3, acts as a coregulator of NF-kappaB to modulate

37 Each TNFAIP3 allele encoded substitutions at non-catalytic re

38 By contrast, a rare human TNFAIP3 allele encoding an A20 protein with 95% loss of

39 Two TNFAIP3 alleles encoding A20 proteins with partial phosp

40 tinct Denisovan hominins and mice revealed a TNFAIP3 allelic series with alterations in the encoded i

41 mor necrosis factor alpha-induced protein 3 (TNFAIP3), also known as A20.

42 tions in multiple genes, including negative (TNFAIP3, also called A20) and positive (CARD11, TRAF2, T

43 heless rapidly countered by the induction of TNFAIP3, an NF-kappaB inhibitor frequently inactivated i

44 factor alpha [TNF-alpha]-induced protein 3 [TNFAIP3]), an inhibitor of the NF-kappaB pathway and a n

45 After stratification by JIA subtype, the TNFAIP3 and C12orf30 variants were associated with oligo

46 GBS exchanges between reporters for TNFAIP3 and FKBP5, a canonical GR-induced target, reveal

47 expression of putative causal genes such as TNFAIP3 and IFNAR1.

48 protein 1 (TNIP1) gene, which interacts with TNFAIP3 and inhibits the TNF-alpha-induced nuclear facto

49 reover, the regulatory effects of miR-19a on TNFAIP3 and NF-kappaB signaling were confirmed using tum

50 6q23 (rs10499194, approximately 150 kb from TNFAIP3 and OLIG3) that was reproducibly associated with

51 susceptibility genes including CD40, TRAF1, TNFAIP3 and PRKCQ.

52 hism responsible for the association between TNFAIP3 and SLE.

53 as associated with downregulation of TNF and TNFAIP3 and upregulation of BAX.

54 deletion of 2 IBD susceptibility genes, A20 (Tnfaip3) and Abin-1 (Tnip1), in intestinal epithelial ce

55 ated genes (such as OAS1/2/3, TLR1/6/10, and TNFAIP3) and also encompass genes (including OCA2 and BN

56 G [P = 0.006], and rs2327832_G [P = 0.03] in TNFAIP3) and one with decreased risk (rs1004446_A in INS

57 F-kB inhibitors (NFKBIA, NFKBID, NFKBIZ, and TNFAIP3) and T-cell exhaustion markers (programmed death

58 The ubiquitin-editing enzyme A20 (TNFAIP3) and the deubiquitinase CYLD are central negativ

59 pha and regulate NF-kappaB signaling (TNIP1, TNFAIP3) and two genes involved in the modulation of Th2

60 on to ZIKV, dengue, and GBS infection; ATF5, TNFAIP3, and BAMB1 were common to ZIKV, dengue, and WNF;

61 d arthritis (RA) susceptibility loci, TAGAP, TNFAIP3, and CCR6, in African American patients with RA.

62 cruitment domain-containing protein 11), A20/TNFAIP3, and CD79A/B.

63 of nonsynonymous coding polymorphisms within TNFAIP3, and found that the A125V coding-change variant

64 ariants, along with tagging polymorphisms in TNFAIP3, and identified a novel African-derived risk hap

65 c loci-HLA-C, IL12B, IL23R, IL23A, IL4/IL13, TNFAIP3, and TNIP1-and ongoing studies are revealing add

66 Functionally, lincRNA- Tnfaip3 appears to mediate both the activation and repre

67 Mutations in A20/TNFAIP3 are associated with a variety of autoimmune dise

68 latory regions of TAGAP and an intronic SNP (TNFAIP3) are potential susceptibility loci in African Am

69 6 genes (KLF4, CENPJ, KLF2, PPP1R15A, FOSB, TNFAIP3) (area under the curve [AUC], 0.98) and 5 immune

70 These results implicate TNFAIP3 as a functionally important endogenous suppresso

71 Our results offer strong evidence for TNFAIP3 as a key regulator of the cytoplasmic signaling

72 ee independent sequencing platforms revealed TNFAIP3 as a relapse biomarker, whose expression was dow

73 in both cancer and immune cells and nominate TNFAIP3 as a synergistic target whose ablation strongly

74 o two outcome groups (P = .037) and revealed TNFAIP3 as part of an optimized four-gene predictor asso

75 M6A, KMT2D, PIK3R1, STAT3, STAT5B, TET2, and TNFAIP3 as recurrently mutated putative drivers using an

76 mor necrosis factor alpha-induced protein 3 (TNFAIP3) as a key endogenous suppressor of ASK1 activati

77 und evidence of two independent signals near TNFAIP3 associated with SLE, including one previously as

78 acts through chromatin looping not only with TNFAIP3, but also with IL20RA, located 680 kb upstream.

79 ll proliferation and V(D)J mutation (CARD11, TNFAIP3, CCND3, ID3, BTG2, and KLHL6) were present in ro

80 ced Tnfaip3 gene expression in DCs in either Tnfaip3(CD11c) or Tnfaip3(LysM) mice dose-dependently co

81 mRNA levels of TNFAIP3, CEBPD and METRNL were inversely associated with

82 Using these approaches, we prioritize TNFAIP3, CEBPD, METRNL and TLN2 as new candidate genes w

83 Both extrinsic death receptor (TNFAIP3, CFLAR, SOD2) and intrinsic mitochondrial (BCL2A

84 CXCL10), immune suppression (PD-L1, NFKB1B, TNFAIP3, CGB), apoptosis (CASP9, FAS, IL-24), and cell g

85 The mouse Tnfaip3 coding variant I325N increases NF- kappaB activa

86 tionally identified a series of unique human TNFAIP3 coding variants linked to the autoimmune genome-

87 Common population-specific TNFAIP3 coding variants that reduce A20's enzyme functio

88 This resultant NF-kappaB/Hmgb1/lincRNA-Tnfaip3 complex can modulate Hmgb1-associated histone mo

89 Hmgb1), assembling a NF-kappaB/Hmgb1/lincRNA-Tnfaip3 complex in macrophages after LPS stimulation.

90 These results establish that variants near TNFAIP3 contribute to differential risk of SLE and RA.

91 Mice harboring Tnfaip3-deficient cDC1s did not develop Th2-driven eosin

92 TNFAIP3-deficient DCs induced HDM-specific TH17 cell dif

93 ressor of ASK1 activation, and we found that TNFAIP3 directly interacts with and deubiquitinates ASK1

94 xpression of a negative immune regulator A20/TNFAIP3 during viral infection that may contribute to th

95 ally expressed in previous studies including TNFAIP3, DUSP2, and IL6.

96 TNFAIP3 encodes A20, a tumor necrosis factor (TNF)-alpha

97 TNFAIP3, encoding the ubiquitin-modifying enzyme A20, is

98 Hepatocyte-specific ablation of Tnfaip3 exacerbated nonalcoholic fatty liver disease- an

99 expression pattern of a regulator molecule, TNFAIP3, exhibited prominent variability between individ

100 Importantly, miR-125a/mir-125b effects on TNFAIP3 expression and NF-kappaB activity were confirmed

101 These data show that the extent of TNFAIP3 expression in DCs controls TH2/TH17 cell differe

102 Levels of A20/TNFAIP3 expression in lung tissue demonstrated that HFD

103 isms in the deubiquitinating (DUB) domain of TNFAIP3: F127C, which is in high-linkage disequilibrium

104 excision of A20/Tnfaip3 was used, generating Tnfaip3(fl/fl) xCd207(+/cre) (Tnfaip3(Lg-KO) ) mice.

105 self-regulatory loop whereby termination of TNFAIP3 function by miR-125 could strengthen and prolong

106 R/NF-kappaB cooperation, suggesting that the TNFAIP3 GBS acts primarily as a docking site in this con

107 ese findings point to variability in the A20/TNFAIP3 gene as a modulator of CAD risk in type 2 diabet

108 ransgenic or adeno-associated virus-mediated TNFAIP3 gene delivery in the liver in both mouse and non

109 The TNFAIP3 gene encodes A20, a cytoplasmic ubiquitin ligase

110 e and inflammatory diseases, variants of the TNFAIP3 gene encoding the ubiquitin-editing enzyme A20 a

111 We demonstrated that reduced Tnfaip3 gene expression in DCs in either Tnfaip3(CD11c)

112 xposed mice with conditional deletion of the Tnfaip3 gene in either myeloid cells (by using the lysoz

113 Thus, TNFAIP3 gene variants represent a kidney and population-

114 Inactivation of the TNFAIP3 gene, encoding the A20 protein, is associated wi

115 cations in autoimmunity; A20, encoded by the TNFAIP3 gene, Lyp encoded by the PTPN22 gene, and the BC

116 mor necrosis factor-alpha-induced protein 3 (TNFAIP3) gene has been associated with psoriasis, rheuma

117 mor necrosis factor alpha-induced protein 3 (Tnfaip3) gene, is an early-primary response gene control

118 Somatic mutations of TNFAIP3 have been observed in the mucosa-associated lymp

119 hic coding variants in AKI we tested a mouse Tnfaip3 hypomorph in a model of ischemia reperfusion inj

120 To investigate the impact of TNFAIP3 hypomorphic coding variants in AKI we tested a m

121 tudied germline and somatic abnormalities of TNFAIP3 in 574 patients with pSS, including 25 with lymp

122 rheumatoid arthritis susceptibility gene A20/Tnfaip3 in mice (A20(myel-KO) mice) triggers a spontaneo

123 is study we investigated the precise role of TNFAIP3 in myeloid cells for the development of TH2- and

124 Inactivation of Tnfaip3 in T cells enhanced anti-tumor efficacy.

125 e genes TNF and TNF-alpha-induced protein 3 (TNFAIP3) in peripheral blood leukocytes.

126 3) and increased TNFalpha-induced protein 3 (TNFAIP3) in Vldlr(-/-) photoreceptors.

127 back inhibitor mRNAs, such as Ier3, Dusp1 or Tnfaip3, in the absence of MK2-dependent TTP neutralizat

128 the IL-17-negative regulation genes, such as TNFAIP3, increased in myeloid cells more after IL-23 inh

129 tiple single nucleotide polymorphisms in the TNFAIP3 interacting protein 1 (TNIP1) gene, which intera

130 treatment, the inflammation repressor TNIP1 (TNFAIP3 interacting protein 1) is phosphorylated by Tank

131 TNF receptor-associated factor (TRAF) 1, and TNFAIP3-interacting protein (TNIP) 3.

132 based on the human SLE susceptibility locus TNFAIP3-interacting protein 1 (TNIP1, also known as ABIN

133 s2233290) at position 151 (Pro-->Ala) in the TNFAIP3-interacting protein 1, TNIP1, confers even stron

134 sic loss of the ubiquitin modifying molecule Tnfaip3, involved in dampening IL-33 signaling, enhanced

135 overed that the negative NF-kappaB regulator TNFAIP3 is a direct target of miR-125a and miR-125b, whi

136 paB and extrinsic apoptosis, confirming that TNFAIP3 is a functionally relevant target of miR-29b.

137 Specifically, induction of lincRNA-Tnfaip3 is required for the transactivation of NF-kappaB

138 A20 (TNFAIP3) is a critical negative regulator of NF-kappaB.

139 mor necrosis factor (TNF)-induced protein 3 (TNFAIP3) is a negative regulator of nuclear factor-kappa

140 r necrosis factor alpha-induced protein 3 or TNFAIP3) is a ubiquitin-editing enzyme that mainly funct

141 tumor necrosis factor a-induced protein 3 or TNFAIP3) is a ubiquitin-editing enzyme that mainly funct

142 The TNF alpha-induced protein 3 (TNFAIP3) is an ubiquitin-modifying enzyme and an essenti

143 rrent mutations in oncogenic drivers such as TNFAIP3, ITPKB, and SOCS1, and a cold TME.

144 nalysis of targeted genes further implicated TNFAIP3, KMT2D, and TRAF3 as recurrent targets of somati

145 Analysis of conditional TNFAIP3 knock-out mice reproduced the wiring of the TNF/

146 Our studies suggest that alterations in TNFAIP3 levels are associated with relapses in MOG-AAD p

147 ditional cohort of patients showed decreased TNFAIP3 levels at relapse compared to remission state in

148 ed, generating Tnfaip3(fl/fl) xCd207(+/cre) (Tnfaip3(Lg-KO) ) mice.

149 In addition, Tnfaip3(Lg-KO) mice harbored increased numbers of IL-12-

150 Blocking either IL-12 or IFNgamma in Tnfaip3(Lg-KO) mice restored Th2 responses, whereas admi

151 We report here that the lincRNA gene lincRNA-Tnfaip3, located at mouse chromosome 10 proximal to the

152 variants in the PTPN22, TRAF1/C5, STAT4, and TNFAIP3 loci.

153 xpression, GR and NF-kappaB occupancy at the TNFAIP3 locus and GR-repressed targets was similar.

154 variants at the multiple disease-associated TNFAIP3 locus in five disease-relevant immune cell lines

155 wide association studies have implicated the TNFAIP3 locus in susceptibility to autoimmune disorders

156 ci including rs10499194 and rs6920220 in the TNFAIP3 locus, rs6679677 in the RSBN1 locus, rs17696736

157 atients with HA20, we show that heterozygous TNFAIP3 loss skews immune repertoires toward lymphocytes

158 xpression in DCs in either Tnfaip3(CD11c) or Tnfaip3(LysM) mice dose-dependently controlled developme

159 to depict how the A125V amino acid change in TNFAIP3 may affect the three-dimensional structure of th

160 RC-derived ITGBL1-enriched EVs stimulate the TNFAIP3-mediated NF-kappaB signaling pathway to activate

161 pe carrying this variant resulted in reduced TNFAIP3 mRNA and A20 protein expression.

162 pathway gene mutations (PIK3CD/PIK3AP1) and TNFAIP3 mutations were seen in 5% and 10% of patients, r

163 y and in the treatment of patients with A20 (TNFAIP3) mutations.

164 Targeting the EVs-ITGBL1-CAFs-TNFAIP3-NF-kappaB signaling axis provides an attractive

165 XPO1, or NF-kB signaling pathway mutations (TNFAIP3, NFKBIE, IKBKB, NFKBIA).

166 as rescue assays and genetic modulation of a TNFAIP3-null model defined the essential role of the TNF

167 Ablation of TNF-alpha-induced protein 3 (TNFAIP3), one of the crucial negative regulators of nucl

168 tase, DUSP1, the ubiquitin-modifying enzyme, TNFAIP3, or the mRNA-destabilizing protein, ZFP36.

169 Both Tnfaip3(OTU) and Tnfaip3(ZF4) mice exhibited increased r

170 ting either A20's deubiquitinating activity (Tnfaip3(OTU) mice) or A20's ZF4 (Tnfaip3(ZF4) mice).

171 kappaB signaling normally in compound mutant Tnfaip3(OTU/ZF4) cells.

172 4149 near IL23R, p = 0.00018; rs9321623 near TNFAIP3, p = 0.00022).

173 LincRNA-Tnfaip3 physically interacts with the high-mobility grou

174 on (ARID1A and MEF2B), NF-kappaB (CARD11 and TNFAIP3), PI3 kinase (PIK3CD, PIK3R1, and MTOR), B-cell

175 s the first report of an association between TNFAIP3 polymorphisms and autoimmunity in African-Americ

176 ive regulators of these pathways (eg, TRAF2, TNFAIP3) promoted resistance.

177 d methylation of cytosine nucleotides in the TNFAIP3 promoter was found to be correlated with this va

178 crosis factor (TNF) alpha-induced protein 3 (TNFAIP3), protein tyrosine phosphatase non-receptor type

179 with variants in 29 other regions, including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2 and

180 We show that three independent SNPs in the TNFAIP3 region (rs13192841, rs2230926 and rs6922466) are

181 A co-occupied intronic TNFAIP3 regulatory element mediated cooperative enhancem

182 /NF-kappaB cooperative induction of a mutant TNFAIP3 reporter harboring the FKBP5 GBS.

183 pression of an miR-29b-refractory isoform of TNFAIP3 restored NF-kappaB and extrinsic apoptosis, conf

184 erse populations, we fully characterized the TNFAIP3 risk haplotype and identified a TT>A polymorphic

185 Childhood-onset RA was associated with TNFAIP3 rs10499194 (OR 0.60 [95% confidence interval 0.4

186 an association between SLE and a variant in TNFAIP3 (rs5029939, meta-analysis P = 2.89 x 10(-12), OR

187 27 SNPs (CCR6 rs3093023, TAGAP rs394581, and TNFAIP3 rs6920220) demonstrated ORs in the opposite dire

188 s were significantly associated with RA: the TNFAIP3 rs719149 A allele (OR 1.22 [95% confidence inter

189 0 patients with paired germline and lymphoma TNFAIP3 sequence data had functional abnormalities of A2

190 sponse of psoriasis to TNF blockers with two TNFAIP3 single-nucleotide polymorphisms (rs2230926 in ex

191 ently mutated tumor suppressor genes such as TNFAIP3, SOCS3 and TNFRSF14.

192 associations between JIA and variants in the TNFAIP3, STAT4, and C12orf30 regions that have previousl

193 ude and direction of the association between TNFAIP3, STAT4, and PTPN22 variants and childhood-onset

194 tor A (VEGFA) pathway directly, and elevated TNFAIP3 suppressed SOCS3 (suppressor of cytokine signali

195 null model defined the essential role of the TNFAIP3 targeting on miR-125a/miR-125b-mediated lymphoma

196 n CD loci (ICOSLG and TNFSF15) and T1D loci (TNFAIP3) that confer UC risk, known UC loci (HERC2 and I

197 wn, the association is generally assigned to TNFAIP3, the closest gene.

198 heterozygous loss-of-function variations in TNFAIP3, the gene encoding the A20 protein.

199 A new study identifies somatic mutations in TNFAIP3, the gene encoding the NF-kappaB inhibitor A20,

200 Along with other associations near TRAF1 and TNFAIP3, this implies a central role for the CD40 signal

201 In light of recently discovered A20/TNFAIP3 (TNFalpha-induced protein 3) single nucleotide p

202 1, POMP, RAG1, SH2D1A, SKIV2L, STAT1, STAT3, TNFAIP3, TNFRSF6/FAS, TNRSF13B/TACI, TOM1, TTC37, and XI

203 1B, CDK5, CDC42SE2, MDM4, NME7, RAB8B, TFE3, TNFAIP3, TNK1, TOP1, VAMP2, and YY1.

204 regulatory role of NF-kappaB-induced lincRNA-Tnfaip3 to act as a coactivator of NF-kappaB for the tra

205 ve generated mice bearing a floxed allele of Tnfaip3 to interrogate A20's roles in regulating B cell

206 Notably, the sub-networks regulated by TNFAIP3, TRAFD1 and PML are involved in innate immune re

207 fully identified several MRs including SOX3, TNFAIP3, TRAFD1, POU3F3, STAT2, and PML that govern the

208 n A20 closely mirrored the expression of the TNFAIP3 transcript, and was inversely related to NF-kapp

209 uced inflammatory responses through inducing Tnfaip3 transcription and controlling the metabolic repr

210 ptor (TLR)-induced inflammation by promoting Tnfaip3 transcription and fine-tuning of metabolic repro

211 While the pathogenic effect of TNFAIP3 truncating variations is clearly established, th

212 The TNFAIP3 (tumor necrosis factor alpha-induced protein 3)

213 thrombomodulin), PROCR (protein C receptor), TNFAIP3 (tumor necrosis factor-alpha-induced protein 3),

214 p = 1.1 x 10(-5) ), including genes, such as TNFAIP3, TYK2, and TNFRSF1A.

215 ith JIA risk or protection were observed for TNFAIP3 variants rs10499194 (OR 0.74 [95% CI 0.61-0.91],

216 Herein, we identified a novel TNFAIP3 variation, p.(Leu236Pro), located in the A20 ova

217 s, Cd207 (Langerin)-mediated excision of A20/Tnfaip3 was used, generating Tnfaip3(fl/fl) xCd207(+/cre

218 mor necrosis factor-alpha-induced protein 3 (TNFAIP3) was identified as a new regulatory component of

219 regulators of NF-kappaB signaling (MYD88 and TNFAIP3) were gained at transformation.

220 Polymorphisms of TNFAIP3, which encodes the A20 protein that plays a key

221 enetrance heterozygous germline mutations in TNFAIP3, which encodes the NF-kappaB regulatory protein

222 Given recent data linking A20 (TNFAIP3) with human B cell lymphomas and systemic lupus

223 try: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYN

224 Both Tnfaip3(OTU) and Tnfaip3(ZF4) mice exhibited increased responses to TNF a

225 g activity (Tnfaip3(OTU) mice) or A20's ZF4 (Tnfaip3(ZF4) mice).

226 overexpression of negative regulators (DUSP, TNFAIP3, ZFP36) and expression of PD-1, CTLA-4, TIGIT, a