Gene Symbol: A20
Description: TNF alpha induced protein 3
Alias: A20, AISBL, OTUD7C, TNFA1P2, tumor necrosis factor alpha-induced protein 3, OTU domain-containing protein 7C, tumor necrosis factor inducible protein A20, tumor necrosis factor, alpha induced protein 3, zinc finger protein A20
Species: human
Products:     A20

Top Publications

  1. Dieude P, Guedj M, Wipff J, Ruiz B, Riemekasten G, Matucci Cerinic M, et al. Association of the TNFAIP3 rs5029939 variant with systemic sclerosis in the European Caucasian population. Ann Rheum Dis. 2010;69:1958-64 pubmed publisher
    ..2×10??), fibrosing alveolitis (pooled OR=2.26 (1.61 to 3.17), p=2.5×10??) and pulmonary arterial hypertension (pooled OR=3.11 (1.86 to 5.17), p=1.3×10??). These results suggest that TNFAIP3 is a genetic susceptibility factor for SSc. ..
  2. Bowes J, Lawrence R, Eyre S, Panoutsopoulou K, Orozco G, Elliott K, et al. Rare variation at the TNFAIP3 locus and susceptibility to rheumatoid arthritis. Hum Genet. 2010;128:627-33 pubmed publisher
  3. Bates J, Lessard C, Leon J, Nguyen T, Battiest L, Rodgers J, et al. Meta-analysis and imputation identifies a 109 kb risk haplotype spanning TNFAIP3 associated with lupus nephritis and hematologic manifestations. Genes Immun. 2009;10:470-7 pubmed publisher
    TNFAIP3 encodes the ubiquitin-modifying enzyme, A20, a key regulator of inflammatory signaling pathways. We previously reported association between TNFAIP3 variants and systemic lupus erythematosus (SLE)...
  4. Shimane K, Kochi Y, Horita T, Ikari K, Amano H, Hirakata M, et al. The association of a nonsynonymous single-nucleotide polymorphism in TNFAIP3 with systemic lupus erythematosus and rheumatoid arthritis in the Japanese population. Arthritis Rheum. 2010;62:574-9 pubmed publisher
    ..TNFAIP3, similar to STAT4 and IRF5, may be a common genetic risk factor for SLE and RA that is shared between the Caucasian and Japanese populations. ..
  5. Komander D, Barford D. Structure of the A20 OTU domain and mechanistic insights into deubiquitination. Biochem J. 2008;409:77-85 pubmed
    The NF-kappaB (nuclear factor kappaB) regulator A20 antagonises IKK [IkappaB (inhibitor of kappaB) kinase] activation by modulating Lys63-linked polyubiquitination of cytokine-receptor-associated factors including TRAF2/6 (tumour-..
  6. Skaug B, Chen J, Du F, He J, Ma A, Chen Z. Direct, noncatalytic mechanism of IKK inhibition by A20. Mol Cell. 2011;44:559-71 pubmed publisher
    b>A20 is a potent anti-inflammatory protein that inhibits NF-?B, and A20 dysfunction is associated with autoimmunity and B cell lymphoma...
  7. Kawasaki A, Ito S, Furukawa H, Hayashi T, Goto D, Matsumoto I, et al. Association of TNFAIP3 interacting protein 1, TNIP1 with systemic lupus erythematosus in a Japanese population: a case-control association study. Arthritis Res Ther. 2010;12:R174 pubmed publisher
    ..is involved in inhibition of nuclear factor-?B (NF-?B) activation by interacting with TNF alpha-induced protein 3, A20 (TNFAIP3), an established susceptibility gene to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA)...
  8. Dieguez Gonzalez R, Calaza M, Perez Pampin E, Balsa A, Blanco F, Canete J, et al. Analysis of TNFAIP3, a feedback inhibitor of nuclear factor-kappaB and the neighbor intergenic 6q23 region in rheumatoid arthritis susceptibility. Arthritis Res Ther. 2009;11:R42 pubmed publisher
    ..Our data are consistent with the hypothesis that several RA genetic factors exist in the 6q23 region, including polymorphisms in the TNFAIP3 gene, like that previously described for systemic lupus erythematosus. ..
  9. Vereecke L, Beyaert R, Van Loo G. Genetic relationships between A20/TNFAIP3, chronic inflammation and autoimmune disease. Biochem Soc Trans. 2011;39:1086-91 pubmed publisher
    b>A20 [also known as TNFAIP3 (tumour necrosis factor ?-induced protein 3)] restricts and terminates inflammatory responses through modulation of the ubiquitination status of central components in NF-?B (nuclear factor ?B), IRF3 (interferon ..

More Information


  1. Kunter U, Daniel S, Arvelo M, Choi J, Shukri T, Patel V, et al. Combined expression of A1 and A20 achieves optimal protection of renal proximal tubular epithelial cells. Kidney Int. 2005;68:1520-32 pubmed
    ..In endothelial cells, the Bcl family member A1 and the zinc finger protein A20 have redundant and dual antiapoptotic and anti-inflammatory effects...
  2. Vendrell J, Ghayad S, Ben Larbi S, Dumontet C, Mechti N, Cohen P. A20/TNFAIP3, a new estrogen-regulated gene that confers tamoxifen resistance in breast cancer cells. Oncogene. 2007;26:4656-67 pubmed
    The zinc-finger protein A20/TNFAIP3, an inhibitor of nuclear factor-kappaB (NF-kappaB) activation, has been shown to protect MCF-7 breast carcinoma cells from TNFalpha-induced apoptosis...
  3. Heyninck K, De Valck D, Vanden Berghe W, Van Criekinge W, Contreras R, Fiers W, et al. The zinc finger protein A20 inhibits TNF-induced NF-kappaB-dependent gene expression by interfering with an RIP- or TRAF2-mediated transactivation signal and directly binds to a novel NF-kappaB-inhibiting protein ABIN. J Cell Biol. 1999;145:1471-82 pubmed
    The zinc finger protein A20 is a tumor necrosis factor (TNF)- and interleukin 1 (IL-1)-inducible protein that negatively regulates nuclear factor-kappa B (NF-kappaB)-dependent gene expression...
  4. He K, Ting A. A20 inhibits tumor necrosis factor (TNF) alpha-induced apoptosis by disrupting recruitment of TRADD and RIP to the TNF receptor 1 complex in Jurkat T cells. Mol Cell Biol. 2002;22:6034-45 pubmed
    ..We show here that the zinc finger protein A20 is an NF-kappaB-inducible gene that can protect the IKKgamma-deficient cells from TNF-induced apoptosis ..
  5. Shembade N, Parvatiyar K, Harhaj N, Harhaj E. The ubiquitin-editing enzyme A20 requires RNF11 to downregulate NF-kappaB signalling. EMBO J. 2009;28:513-22 pubmed publisher
    ..RNF11 interacted with the NF-kappaB inhibitor A20 and its regulatory protein TAX1BP1 in a stimulus-dependent manner...
  6. Wang K, Baldassano R, Zhang H, Qu H, Imielinski M, Kugathasan S, et al. Comparative genetic analysis of inflammatory bowel disease and type 1 diabetes implicates multiple loci with opposite effects. Hum Mol Genet. 2010;19:2059-67 pubmed publisher
  7. Oshima S, Turer E, Callahan J, Chai S, Advincula R, Barrera J, et al. ABIN-1 is a ubiquitin sensor that restricts cell death and sustains embryonic development. Nature. 2009;457:906-9 pubmed publisher
    ..ABIN-1 (A20 binding and inhibitor of NF-kappaB) is a novel protein that is thought to inhibit NF-kappaB signalling...
  8. Chng H, Camplejohn R, Stone M, Hart I, Nicholson L. A new role for the anti-apoptotic gene A20 in angiogenesis. Exp Cell Res. 2006;312:2897-907 pubmed
    b>A20 is a negative regulator of NF-kappaB activation and thus a potential therapeutic tool for the treatment of diseases where apoptosis and/or inflammatory responses are part of the pathogenic process...
  9. Parvatiyar K, Harhaj E. Regulation of inflammatory and antiviral signaling by A20. Microbes Infect. 2011;13:209-15 pubmed publisher
    The deubiquitinating enzyme A20 (also known as TNFAIP3) is essential for maintaining immune homeostasis. A20 is a key regulator of inflammatory, antiviral and apoptotic signaling pathways...
  10. Bremm A, Freund S, Komander D. Lys11-linked ubiquitin chains adopt compact conformations and are preferentially hydrolyzed by the deubiquitinase Cezanne. Nat Struct Mol Biol. 2010;17:939-47 pubmed publisher
    ..Our data highlight the intrinsic specificity of the ubiquitin system that extends to Lys11-linked chains and emphasize that differentially linked polyubiquitin chains must be regarded as independent post-translational modifications. ..
  11. Kawasaki A, Ito I, Ito S, Hayashi T, Goto D, Matsumoto I, et al. Association of TNFAIP3 polymorphism with susceptibility to systemic lupus erythematosus in a Japanese population. J Biomed Biotechnol. 2010;2010:207578 pubmed publisher
    ..013). These results indicated that TNFAIP3 is a susceptibility gene to SLE both in the Caucasian and Asian populations. ..
  12. Xiong Y, Qiu F, Piao W, Song C, Wahl L, Medvedev A. Endotoxin tolerance impairs IL-1 receptor-associated kinase (IRAK) 4 and TGF-beta-activated kinase 1 activation, K63-linked polyubiquitination and assembly of IRAK1, TNF receptor-associated factor 6, and IkappaB kinase gamma and increases A20 express. J Biol Chem. 2011;286:7905-16 pubmed publisher
    ..Deficiencies in these signaling events in LPS-tolerant cells coincided with increased expression of A20, an essential deubiquitination enzyme, and sustained A20-IRAK1 associations...
  13. Evans P, Ovaa H, Hamon M, Kilshaw P, Hamm S, Bauer S, et al. Zinc-finger protein A20, a regulator of inflammation and cell survival, has de-ubiquitinating activity. Biochem J. 2004;378:727-34 pubmed
    ..The zinc-finger protein A20 has dual functions in inhibiting NF-kappaB activation and suppressing apoptosis...
  14. Malynn B, Ma A. A20 takes on tumors: tumor suppression by an ubiquitin-editing enzyme. J Exp Med. 2009;206:977-80 pubmed publisher
    ..A new study identifies somatic mutations in TNFAIP3, the gene encoding the NF-kappaB inhibitor A20, in Hodgkin lymphomas and primary mediastinal lymphomas...
  15. Duwel M, Welteke V, Oeckinghaus A, Baens M, Kloo B, Ferch U, et al. A20 negatively regulates T cell receptor signaling to NF-kappaB by cleaving Malt1 ubiquitin chains. J Immunol. 2009;182:7718-28 pubmed publisher
    ..Further, the ubiquitin-editing enzyme A20 was recently suggested to suppress T cell activation, but molecular targets for A20 remain elusive...
  16. Bellail A, Olson J, Yang X, Chen Z, Hao C. A20 ubiquitin ligase-mediated polyubiquitination of RIP1 inhibits caspase-8 cleavage and TRAIL-induced apoptosis in glioblastoma. Cancer Discov. 2012;2:140-55 pubmed publisher
    ..We show that A20-mediated ubiquitination inhibits caspase-8 cleavage and TRAIL-induced apoptosis in glioblastoma through 2 signaling ..
  17. Han J, Zheng H, Cui Y, Sun L, Ye D, Hu Z, et al. Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nat Genet. 2009;41:1234-7 pubmed publisher
    ..This study not only advances our understanding of the genetic basis of SLE but also highlights the value of performing GWAS in diverse ancestral populations. ..
  18. Lodolce J, Kolodziej L, Rhee L, Kariuki S, Franek B, McGreal N, et al. African-derived genetic polymorphisms in TNFAIP3 mediate risk for autoimmunity. J Immunol. 2010;184:7001-9 pubmed publisher
    ..This is the first report of an association between TNFAIP3 polymorphisms and autoimmunity in African-Americans. ..
  19. Novak U, Rinaldi A, Kwee I, Nandula S, Rancoita P, Compagno M, et al. The NF-{kappa}B negative regulator TNFAIP3 (A20) is inactivated by somatic mutations and genomic deletions in marginal zone lymphomas. Blood. 2009;113:4918-21 pubmed publisher
    ..deletions of the chromosomal band 6q23, involving the tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20) gene, a negative regulator of NF-kappaB, were described in ocular adnexal MZL, suggesting a role for A20 as a ..
  20. Braun F, Grabarczyk P, Möbs M, Braun F, Eberle J, Beyer M, et al. Tumor suppressor TNFAIP3 (A20) is frequently deleted in Sézary syndrome. Leukemia. 2011;25:1494-501 pubmed publisher
    ..We identified bi- and monoallelic deletions of the tumor necrosis factor-?-induced protein 3 gene (TNFAIP3; A20) in a high proportion of SS patients as well as biallelic A20 deletion in the SS-derived cell line SeAx...
  21. Elsby L, Orozco G, Denton J, Worthington J, Ray D, Donn R. Functional evaluation of TNFAIP3 (A20) in rheumatoid arthritis. Clin Exp Rheumatol. 2010;28:708-14 pubmed
    ..This is the first observation of TNFAIP3 protein expression in RA and OA synovium. In vitro analysis of 6q23 intergenic SNPs supports the possibility of the functional regulation of TNFAIP3. ..
  22. Cooper J, Stroka D, Brostjan C, Palmetshofer A, Bach F, Ferran C. A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism. J Biol Chem. 1996;271:18068-73 pubmed
    The A20 gene product is a novel zinc finger protein originally described as a tumor necrosis factor alpha (TNF)-inducible early response gene in human umbilical vein endothelial cells (HUVEC)...
  23. Breckpot K, Aerts Toegaert C, Heirman C, Peeters U, Beyaert R, Aerts J, et al. Attenuated expression of A20 markedly increases the efficacy of double-stranded RNA-activated dendritic cells as an anti-cancer vaccine. J Immunol. 2009;182:860-70 pubmed
    b>A20 is a zinc finger protein with ubiquitin-modifying activity...
  24. Cai L, Wang Z, Lu W, Han J, Sun L, Du W, et al. A single-nucleotide polymorphism of the TNFAIP3 gene is associated with systemic lupus erythematosus in Chinese Han population. Mol Biol Rep. 2010;37:389-94 pubmed publisher
    ..Our findings suggest that SNP rs2230926 in the TNFAIP3 might be a common genetic factor for SLE within different populations in terms of Chinese Han and European population. ..
  25. Coornaert B, Baens M, Heyninck K, Bekaert T, Haegman M, Staal J, et al. T cell antigen receptor stimulation induces MALT1 paracaspase-mediated cleavage of the NF-kappaB inhibitor A20. Nat Immunol. 2008;9:263-71 pubmed publisher
    ..Here we show that T cell antigen receptor stimulation induced recruitment of the NF-kappaB inhibitor A20 into a complex of MALT1 and the adaptor protein Bcl-10, leading to MALT1-mediated processing of A20...
  26. Gon Y, Asai Y, Hashimoto S, Mizumura K, Jibiki I, Machino T, et al. A20 inhibits toll-like receptor 2- and 4-mediated interleukin-8 synthesis in airway epithelial cells. Am J Respir Cell Mol Biol. 2004;31:330-6 pubmed
    The zinc finger protein A20 is encoded by an immediate early response gene and acts as an inhibitor of nuclear factor (NF)-kappaB-dependent gene expression induced by different stimuli, including tumor necrosis factor-alpha (TNF-alpha) ..
  27. Lee E, Boone D, Chai S, Libby S, Chien M, Lodolce J, et al. Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice. Science. 2000;289:2350-4 pubmed
    b>A20 is a cytoplasmic zinc finger protein that inhibits nuclear factor kappaB (NF-kappaB) activity and tumor necrosis factor (TNF)-mediated programmed cell death (PCD)...
  28. Kato M, Sanada M, Kato I, Sato Y, Takita J, Takeuchi K, et al. Frequent inactivation of A20 in B-cell lymphomas. Nature. 2009;459:712-6 pubmed publisher
    b>A20 is a negative regulator of the NF-kappaB pathway and was initially identified as being rapidly induced after tumour-necrosis factor-alpha stimulation...
  29. Elder J. Genome-wide association scan yields new insights into the immunopathogenesis of psoriasis. Genes Immun. 2009;10:201-9 pubmed publisher
  30. Honma K, Tsuzuki S, Nakagawa M, Karnan S, Aizawa Y, Kim W, et al. TNFAIP3 is the target gene of chromosome band 6q23.3-q24.1 loss in ocular adnexal marginal zone B cell lymphoma. Genes Chromosomes Cancer. 2008;47:1-7 pubmed
    ..TNFAIP3 is an inhibitor of NF-kB signaling so that loss of this gene may play an important role in lymphomagenesis and suggests that TNFAIP3 may act as a tumor suppressor gene in ocular adnexal marginal zone B cell lymphoma. ..
  31. Bi Y, Zeng N, Chanudet E, Huang Y, Hamoudi R, Liu H, et al. A20 inactivation in ocular adnexal MALT lymphoma. Haematologica. 2012;97:926-30 pubmed publisher
    Recent studies showed A20 inactivation by deletion, mutation and promoter methylation in ocular adnexal mucosa-associated lymphoid tissue lymphoma...
  32. De Valck D, Heyninck K, Van Criekinge W, Vandenabeele P, Fiers W, Beyaert R. A20 inhibits NF-kappaB activation independently of binding to 14-3-3 proteins. Biochem Biophys Res Commun. 1997;238:590-4 pubmed
    The A20 protein, which belongs to a class of Cys2/Cys2 zinc finger proteins, has been characterized as an inhibitor of NF-kappaB activation...
  33. Schmitz R, Hansmann M, Bohle V, Martin Subero J, Hartmann S, Mechtersheimer G, et al. TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma. J Exp Med. 2009;206:981-9 pubmed publisher
    ..NF-kappaB activation through various stimuli is negatively regulated by the zinc finger protein A20. To determine whether A20 contributes to the pathogenesis of cHL, we sequenced TNFAIP3, encoding A20, in ..
  34. Zhong H, Li X, Li M, Hao L, Chen R, Xiang K, et al. Replicated associations of TNFAIP3, TNIP1 and ETS1 with systemic lupus erythematosus in a southwestern Chinese population. Arthritis Res Ther. 2011;13:R186 pubmed publisher
    ..The replication analysis indicates that TNFAIP3, ETS1 and TNIP1 are probably common susceptibility genes for SLE in Chinese populations, and they may contribute to the pathogenesis of multiple SLE subphenotypes. ..
  35. Gallagher J, Howlin J, McCarthy C, Murphy E, Bresnihan B, Fitzgerald O, et al. Identification of Naf1/ABIN-1 among TNF-alpha-induced expressed genes in human synoviocytes using oligonucleotide microarrays. FEBS Lett. 2003;551:8-12 pubmed
    ..The regulation of Nef-associated factor-1 (Naf1), an A20-binding, nuclear factor kappa B (NFkappaB) inhibitory protein was probed further given its putative role as an ..
  36. Nair R, Duffin K, Helms C, Ding J, Stuart P, Goldgar D, et al. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet. 2009;41:199-204 pubmed publisher
    ..Our results expand the catalog of genetic loci implicated in psoriasis susceptibility and suggest priority targets for study in other auto-immune disorders. ..
  37. Musone S, Taylor K, Nititham J, Chu C, Poon A, Liao W, et al. Sequencing of TNFAIP3 and association of variants with multiple autoimmune diseases. Genes Immun. 2011;12:176-82 pubmed publisher
    The TNFAIP3 locus at 6q23, encoding A20, has been associated with multiple autoimmune diseases (AIDs)...
  38. Lin R, Yang L, Nakhaei P, Sun Q, Sharif Askari E, Julkunen I, et al. Negative regulation of the retinoic acid-inducible gene I-induced antiviral state by the ubiquitin-editing protein A20. J Biol Chem. 2006;281:2095-103 pubmed
    ..In the present study, we demonstrate that the NF-kappaB-inducible, anti-apoptotic protein A20 efficiently blocks RIG-I-mediated activation of NF-kappaB-, IRF-3-, and IRF-7-dependent promoters but only weakly ..
  39. Fung E, Smyth D, Howson J, Cooper J, Walker N, Stevens H, et al. Analysis of 17 autoimmune disease-associated variants in type 1 diabetes identifies 6q23/TNFAIP3 as a susceptibility locus. Genes Immun. 2009;10:188-91 pubmed publisher
    ..70 x 10(-3) to 3.20 x 10(-5). These findings extend our knowledge of susceptibility locus sharing across different autoimmune diseases, and provide convincing evidence that the RA/SLE locus 6q23/TNFAIP3 is a newly identified T1D locus. ..
  40. Adrianto I, Wen F, Templeton A, Wiley G, King J, Lessard C, et al. Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus. Nat Genet. 2011;43:253-8 pubmed publisher
    ..TNFAIP3, encoding the ubiquitin-modifying enzyme A20, is an established susceptibility locus for SLE...
  41. Mabilleau G, Chappard D, Sabokbar A. Role of the A20-TRAF6 axis in lipopolysaccharide-mediated osteoclastogenesis. J Biol Chem. 2011;286:3242-9 pubmed publisher
    ..Recently, the role of the deubiquitinating protease A20 in regulating the LPS response in various organs was reported...
  42. Strange A, Capon F, Spencer C, Knight J, Weale M, Allen M, et al. A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat Genet. 2010;42:985-90 pubmed publisher
    ..Our findings implicate pathways that integrate epidermal barrier dysfunction with innate and adaptive immune dysregulation in psoriasis pathogenesis. ..
  43. Wang Q, Yuan L, Liu Z, Yin J, Jiang X, Lu J. Expression of A20 is reduced in pancreatic cancer tissues. J Mol Histol. 2012;43:319-25 pubmed publisher
    b>A20 protein plays essential roles in tumorigenesis, but its value for diagnosis of pancreatic cancer remains unclear. Our aim was to determine whether A20 is a potential biomarker for the diagnosis of pancreatic cancer...
  44. Li H, Liu Q, Hou S, Du L, Zhou Q, Zhou Y, et al. TNFAIP3 gene polymorphisms confer risk for Behcet's disease in a Chinese Han population. Hum Genet. 2013;132:293-300 pubmed publisher
    ..53-0.87]) and A allele (p (c) = 0.025, OR [95% CI] 0.72 [0.57-0.91]) were observed in BD patients. This study identified one strong risk SNP rs9494885 and two weak risk SNPs rs10499194 and rs7753873 of TNFAIP3 in Chinese Han BD patients. ..
  45. Yamaguchi N, Oyama M, Kozuka Hata H, Inoue J. Involvement of A20 in the molecular switch that activates the non-canonical NF-?B pathway. Sci Rep. 2013;3:2568 pubmed publisher
    ..Here, we show that A20, a ubiquitin-editing enzyme, promotes efficient activation of the non-canonical pathway independent of its ..
  46. Zhang S, Kovalenko A, Cantarella G, Wallach D. Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation. Immunity. 2000;12:301-11 pubmed
    ..It also induces binding of NEMO to the signaling inhibitor A20, and recruitment of A20 to the receptor...
  47. Wertz I, O Rourke K, Zhou H, Eby M, Aravind L, Seshagiri S, et al. De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Nature. 2004;430:694-9 pubmed
    ..to downregulate NF-kappaB transcriptional activity results in chronic inflammation and cell death, as observed in A20-deficient mice. A20 is a potent inhibitor of NF-kappaB signalling, but its mechanism of action is unknown...
  48. De Valck D, Jin D, Heyninck K, Van de Craen M, Contreras R, Fiers W, et al. The zinc finger protein A20 interacts with a novel anti-apoptotic protein which is cleaved by specific caspases. Oncogene. 1999;18:4182-90 pubmed
    b>A20 is a Cys2/Cys2 zinc finger protein which is induced by a variety of inflammatory stimuli and which has been characterized as an inhibitor of cell death by a yet unknown mechanism...
  49. Musone S, Taylor K, Lu T, Nititham J, Ferreira R, Ortmann W, et al. Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus. Nat Genet. 2008;40:1062-4 pubmed publisher
    The TNFAIP3 (tumor necrosis factor alpha-induced protein 3) gene encodes a ubiquitin editing enzyme, A20, that restricts NF-kappaB-dependent signaling and prevents inflammation...
  50. Dixit V, Green S, Sarma V, Holzman L, Wolf F, O Rourke K, et al. Tumor necrosis factor-alpha induction of novel gene products in human endothelial cells including a macrophage-specific chemotaxin. J Biol Chem. 1990;265:2973-8 pubmed
    ..Interleukin-1 beta and lipopolysaccharide are also potent inducers. Nuclear run-on studies revealed that in most cases induction by TNF is mediated largely at the transcriptional level. ..
  51. Schumacher M, Schmitz R, Brune V, Tiacci E, Döring C, Hansmann M, et al. Mutations in the genes coding for the NF-?B regulating factors I?B? and A20 are uncommon in nodular lymphocyte-predominant Hodgkin's lymphoma. Haematologica. 2010;95:153-7 pubmed publisher
    ..mutations in the NFKBIA and TNFAIP3 genes, coding for the negative NF-kappaB regulators IkappaBalpha and A20, respectively, contribute to NF-kappaB activation...
  52. Tokunaga F, Nishimasu H, Ishitani R, Goto E, Noguchi T, Mio K, et al. Specific recognition of linear polyubiquitin by A20 zinc finger 7 is involved in NF-?B regulation. EMBO J. 2012;31:3856-70 pubmed publisher
    ..However, the regulatory mechanism of LUBAC-mediated NF-?B activation remains elusive. Here, we show that A20 suppresses LUBAC-mediated NF-?B activation by binding linear polyubiquitin via the C-terminal seventh zinc finger (..
  53. Komander D, Reyes Turcu F, Licchesi J, Odenwaelder P, Wilkinson K, Barford D. Molecular discrimination of structurally equivalent Lys 63-linked and linear polyubiquitin chains. EMBO Rep. 2009;10:466-73 pubmed publisher
    ..Our results highlight remarkable specificity determinants within the ubiquitin system. ..
  54. Yu L, Miao H, Hou Y, Zhang B, Guo L. Neuroprotective effect of A20 on TNF-induced postischemic apoptosis. Neurochem Res. 2006;31:21-32 pubmed
    ..TNF is critically involved in such neuronal apoptosis mediated by caspase pathways. A20 can inhibit TNF-induced apoptosis in many cell types...
  55. Vincenz C, Dixit V. 14-3-3 proteins associate with A20 in an isoform-specific manner and function both as chaperone and adapter molecules. J Biol Chem. 1996;271:20029-34 pubmed
    b>A20, a novel zinc finger protein, is an inhibitor of tumor necrosis factor-induced apoptosis. The mechanism by which A20 exerts its protective effect is currently unknown...
  56. Malinverni C, Unterreiner A, Staal J, Demeyer A, Galaup M, Luyten M, et al. Cleavage by MALT1 induces cytosolic release of A20. Biochem Biophys Res Commun. 2010;400:543-7 pubmed publisher
    The MALT1 paracaspase has arginine-directed proteolytic activity. A20 is a dual ubiquitin-editing enzyme involved in termination of NF-?B signaling...
  57. Giulino L, Mathew S, Ballon G, Chadburn A, Barouk S, Antonicelli G, et al. A20 (TNFAIP3) genetic alterations in EBV-associated AIDS-related lymphoma. Blood. 2011;117:4852-4 pubmed publisher
    b>A20, a negative regulator of NF-?B, has been implicated as a tumor suppressor gene in multiple types of B-cell lymphoma. AIDS-related lymphomas (ARLs) are high-grade B-cell lymphomas that are frequently associated with EBV infection...
  58. Dong G, Chanudet E, Zeng N, Appert A, Chen Y, Au W, et al. A20, ABIN-1/2, and CARD11 mutations and their prognostic value in gastrointestinal diffuse large B-cell lymphoma. Clin Cancer Res. 2011;17:1440-51 pubmed publisher
    ..Activating mutations of CARD11 and inactivating mutations of A20 are frequent events in DLBCL...
  59. Lin S, Chung J, Lamothe B, Rajashankar K, Lu M, Lo Y, et al. Molecular basis for the unique deubiquitinating activity of the NF-kappaB inhibitor A20. J Mol Biol. 2008;376:526-40 pubmed publisher
    ..b>A20 is a specific feedback inhibitor of NF-kappaB activation in these pathways that possesses dual ubiquitin-editing ..
  60. Kochi Y, Okada Y, Suzuki A, Ikari K, Terao C, Takahashi A, et al. A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility. Nat Genet. 2010;42:515-9 pubmed publisher
    ..Moreover, CCR6DNP was associated with susceptibility to Graves' and Crohn's diseases. These results suggest that CCR6 is critically involved in IL-17-driven autoimmunity in human diseases. ..
  61. Heyninck K, Beyaert R. The cytokine-inducible zinc finger protein A20 inhibits IL-1-induced NF-kappaB activation at the level of TRAF6. FEBS Lett. 1999;442:147-50 pubmed
    The zinc finger protein A20 is encoded by an immediate early response gene whose expression is induced by different inflammatory stimuli, including interleukin-1 (IL-1)...
  62. Parvatiyar K, Barber G, Harhaj E. TAX1BP1 and A20 inhibit antiviral signaling by targeting TBK1-IKKi kinases. J Biol Chem. 2010;285:14999-5009 pubmed publisher
    ..Recent studies have described the ubiquitin-editing enzyme A20 as a negative regulator of IRF3 signaling by associating with TBK1-IKKi; however, the regulatory mechanism of A20 ..
  63. Guo Q, Dong H, Liu X, Wang C, Liu N, Zhang J, et al. A20 is overexpressed in glioma cells and may serve as a potential therapeutic target. Expert Opin Ther Targets. 2009;13:733-41 pubmed publisher
    b>A20 is a TNF-inducible primary response gene, which has been found to have antiapoptotic function in several cancer cells...
  64. Hammer G, Turer E, Taylor K, Fang C, Advincula R, Oshima S, et al. Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis. Nat Immunol. 2011;12:1184-93 pubmed publisher
    ..Here we show that mice lacking the ubiquitin-editing molecule A20 specifically in DCs spontaneously showed DC activation and population expansion of activated T cells...
  65. Song H, Rothe M, Goeddel D. The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-kappaB activation. Proc Natl Acad Sci U S A. 1996;93:6721-5 pubmed
    ..Here we show that TRAF1 and TRAF2 interact with A20, a zinc finger protein, whose expression is induced by agents that activate NF-kappaB...
  66. Shembade N, Harhaj N, Parvatiyar K, Copeland N, Jenkins N, Matesic L, et al. The E3 ligase Itch negatively regulates inflammatory signaling pathways by controlling the function of the ubiquitin-editing enzyme A20. Nat Immunol. 2008;9:254-62 pubmed publisher
    The ubiquitin-editing enzyme A20 is a critical negative regulator of inflammation and cytokine-mediated activation of the transcription factor NF-kappaB; however, little is known about the mechanisms of A20-mediated inactivation of ..
  67. Raychaudhuri S, Remmers E, Lee A, Hackett R, Guiducci C, Burtt N, et al. Common variants at CD40 and other loci confer risk of rheumatoid arthritis. Nat Genet. 2008;40:1216-23 pubmed publisher
    ..1 x 10(-7) overall), CDK6 (rs42041, P = 0.010 replication, P = 4.0 x 10(-6) overall), PRKCQ (rs4750316, P = 0.0078 replication, P = 4.4 x 10(-6) overall), and KIF5A-PIP4K2C (rs1678542, P = 0.0026 replication, P = 8.8 x 10(-8) overall). ..
  68. De Valck D, Heyninck K, Van Criekinge W, Contreras R, Beyaert R, Fiers W. A20, an inhibitor of cell death, self-associates by its zinc finger domain. FEBS Lett. 1996;384:61-4 pubmed
    b>A20 is a primary response gene which is induced after monocyte adherence or cytokine stimulation of a variety of cells...
  69. Boone D, Turer E, Lee E, Ahmad R, Wheeler M, Tsui C, et al. The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses. Nat Immunol. 2004;5:1052-60 pubmed
    b>A20 is a cytoplasmic protein required for the termination of tumor necrosis factor (TNF)-induced signals...
  70. Koumakis E, Giraud M, Dieude P, Cohignac V, Cuomo G, Airo P, et al. Brief report: candidate gene study in systemic sclerosis identifies a rare and functional variant of the TNFAIP3 locus as a risk factor for polyautoimmunity. Arthritis Rheum. 2012;64:2746-52 pubmed publisher
    ..Our results support the implication of rare/low-frequency functional variants and the critical role of A20 in autoimmunity.
  71. Vereecke L, Beyaert R, Van Loo G. The ubiquitin-editing enzyme A20 (TNFAIP3) is a central regulator of immunopathology. Trends Immunol. 2009;30:383-91 pubmed publisher
    ..In this context, the intracellular ubiquitin-editing protein A20 (also known as Tumor Necrosis Factor Alpha-Induced Protein 3 or TNFAIP3) is a key player in the negative feedback ..
  72. Daniel S, Arvelo M, Patel V, Longo C, Shrikhande G, Shukri T, et al. A20 protects endothelial cells from TNF-, Fas-, and NK-mediated cell death by inhibiting caspase 8 activation. Blood. 2004;104:2376-84 pubmed
    b>A20 is a stress response gene in endothelial cells (ECs)...
  73. Heyninck K, Kreike M, Beyaert R. Structure-function analysis of the A20-binding inhibitor of NF-kappa B activation, ABIN-1. FEBS Lett. 2003;536:135-40 pubmed
    ..Among others, the NF-kappa B-dependent zinc finger protein A20 is involved in the negative feedback regulation of NF-kappa B activation in response to tumor necrosis ..
  74. Plenge R, Cotsapas C, Davies L, Price A, de Bakker P, Maller J, et al. Two independent alleles at 6q23 associated with risk of rheumatoid arthritis. Nat Genet. 2007;39:1477-82 pubmed
    ..We show that these two SNP associations are statistically independent, are each reproducible in the comparison of our data and WTCCC data, and define risk and protective haplotypes for rheumatoid arthritis at 6q23. ..
  75. Song C, Liu Z, Huang S, Zheng P, Yang P. Probiotics promote endocytic allergen degradation in gut epithelial cells. Biochem Biophys Res Commun. 2012;426:135-40 pubmed publisher
    ..The ubiquitin E3 ligase A20 (A20) plays a role in the endocytic protein degradation in the cells...
  76. Boonyasrisawat W, Eberle D, Bacci S, Zhang Y, Nolan D, Gervino E, et al. Tag polymorphisms at the A20 (TNFAIP3) locus are associated with lower gene expression and increased risk of coronary artery disease in type 2 diabetes. Diabetes. 2007;56:499-505 pubmed
    b>A20 or tumor necrosis factor (TNF)-induced protein 3 (TNFAIP3) is a negative regulator of nuclear factor-kappaB (NF-kappaB)...
  77. Prahalad S, Hansen S, Whiting A, Guthery S, Clifford B, McNally B, et al. Variants in TNFAIP3, STAT4, and C12orf30 loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis. Arthritis Rheum. 2009;60:2124-30 pubmed publisher
    ..Our results suggest that clinically distinct autoimmune phenotypes share common genetic susceptibility factors. ..
  78. Wang C, Wang Y, Fan C, Xu F, Sun W, Liu Y, et al. miR-29c targets TNFAIP3, inhibits cell proliferation and induces apoptosis in hepatitis B virus-related hepatocellular carcinoma. Biochem Biophys Res Commun. 2011;411:586-92 pubmed publisher
    ..Thus miR-29c and TNFAIP3 represent key diagnostic markers and potential therapeutic targets for the prevention and treatment of HBV infection. ..
  79. Mauro C, Pacifico F, Lavorgna A, Mellone S, Iannetti A, Acquaviva R, et al. ABIN-1 binds to NEMO/IKKgamma and co-operates with A20 in inhibiting NF-kappaB. J Biol Chem. 2006;281:18482-8 pubmed
    ..Here we identified ABIN-1 (A20 binding inhibitor of NF-kappaB) as a NEMO/IKKgamma-interacting protein...
  80. Dong B, Lv G, Wang Q, Wei F, Bellail A, Hao C, et al. Targeting A20 enhances TRAIL-induced apoptosis in hepatocellular carcinoma cells. Biochem Biophys Res Commun. 2012;418:433-8 pubmed publisher
    b>A20 was initially identified as a primary gene product following TNF ? treatment in human umbilical vein endothelial cells...
  81. Nomoto J, Hiramoto N, Kato M, Sanada M, Maeshima A, Taniguchi H, et al. Deletion of the TNFAIP3/A20 gene detected by FICTION analysis in classical Hodgkin lymphoma. BMC Cancer. 2012;12:457 pubmed publisher
    The TNFAIP3 gene, which encodes a ubiquitin-modifying enzyme (A20) involved in the negative regulation of NF-?B signaling, is frequently inactivated by gene deletions/mutations in a variety of B-cell malignancies...
  82. Honma K, Tsuzuki S, Nakagawa M, Tagawa H, Nakamura S, Morishima Y, et al. TNFAIP3/A20 functions as a novel tumor suppressor gene in several subtypes of non-Hodgkin lymphomas. Blood. 2009;114:2467-75 pubmed publisher
    ..shown that chromosome 6q was frequently deleted in ocular marginal zone B-cell lymphoma and identified TNFAIP3/A20, a negative regulator of NF-kappaB pathways, as the primary target for 6q deletion...
  83. Verhelst K, Carpentier I, Kreike M, Meloni L, Verstrepen L, Kensche T, et al. A20 inhibits LUBAC-mediated NF-?B activation by binding linear polyubiquitin chains via its zinc finger 7. EMBO J. 2012;31:3845-55 pubmed publisher
    ..However, the mechanisms that regulate linear ubiquitination are still unknown. Here, we show that A20 is rapidly recruited to NEMO and LUBAC upon TNF stimulation and that A20 inhibits LUBAC-induced NF-?B activation ..
  84. Opipari A, Boguski M, Dixit V. The A20 cDNA induced by tumor necrosis factor alpha encodes a novel type of zinc finger protein. J Biol Chem. 1990;265:14705-8 pubmed
    We have previously identified in endothelial cells a gene product designated A20, that is rapidly and profoundly induced by tumor necrosis factor alpha (Dixit, V. M., Green, S., Sarma, V., Holzman, L. B., Wolf, F. W., O'Rourke, K...
  85. Folco E, Rocha V, Lopez Ilasaca M, Libby P. Adiponectin inhibits pro-inflammatory signaling in human macrophages independent of interleukin-10. J Biol Chem. 2009;284:25569-75 pubmed publisher
    ..genes with established anti-inflammatory properties revealed that adiponectin augmented the expression of A20, suppressor of cytokine signaling (SOCS) 3, B-cell CLL/lymphoma (BCL) 3, TNF receptor-associated factor (TRAF) 1, ..
  86. Oshima N, Ishihara S, Rumi M, Aziz M, Mishima Y, Kadota C, et al. A20 is an early responding negative regulator of Toll-like receptor 5 signalling in intestinal epithelial cells during inflammation. Clin Exp Immunol. 2010;159:185-98 pubmed publisher
    ..receptor (TLR)-mediated inflammatory responses and restore immune system balance, including the zinc-finger protein A20, a negative regulator of TLR signalling that inhibits nuclear factor kappa B (NF-kappaB) activity...
  87. Graham R, Cotsapas C, Davies L, Hackett R, Lessard C, Leon J, et al. Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus. Nat Genet. 2008;40:1059-61 pubmed publisher
    ..These results establish that variants near TNFAIP3 contribute to differential risk of SLE and RA. ..
  88. Kolodziej L, Lodolce J, Chang J, Schneider J, Grimm W, Bartulis S, et al. TNFAIP3 maintains intestinal barrier function and supports epithelial cell tight junctions. PLoS ONE. 2011;6:e26352 pubmed publisher
    ..These in vivo and in vitro studies support the role of TNFAIP3 in promoting intestinal epithelial barrier integrity and demonstrate its novel ability to maintain intestinal homeostasis through tight junction protein regulation. ..
  89. Fries K, Miller W, Raab Traub N. The A20 protein interacts with the Epstein-Barr virus latent membrane protein 1 (LMP1) and alters the LMP1/TRAF1/TRADD complex. Virology. 1999;264:159-66 pubmed publisher
    ..b>A20, which is induced by LMP1 through NF-kB, can block NF-kB activation from both domains of LMP1 and inhibit JNK ..