Tumor necrosis factor, alpha-induced protein 3 is a protein that in humans is encoded by the TNFAIP3gene.[1][2]
This gene was identified as a gene whose expression is rapidly induced by the tumor necrosis factor (TNF). The protein encoded by this gene is a zinc finger protein, and has been shown to inhibit NF-kappa B activation as well as TNF-mediated apoptosis. Knockout studies of a similar gene in mice suggested that this gene is critical for limiting inflammation by terminating TNF-induced NF-kappa B responses.[2]
The TNFAIP3 locus is implicated as a positively associated factor in rheumatoid arthritis (RA). The rs5029937 (T) and the rs6920220 (A) SNPs increase risk of RA by 20 to 40% respectively.[11] A third SNP, rs10499194 (T) is found less often in rheumatoid arthritis but this negative association may not be statistically meaningful.
Other diseases
An association with infantile onset intractable inflammatory bowel disease has also been reported.[12]
References
↑Opipari AW Jr; Boguski MS; Dixit VM (October 1990). "The A20 cDNA induced by tumor necrosis factor alpha encodes a novel type of zinc finger protein". J Biol Chem. 265 (25): 14705–8. PMID2118515.
↑ 5.05.1Heyninck, K; Beyaert R (January 1999). "The cytokine-inducible zinc finger protein A20 inhibits IL-1-induced NF-kappaB activation at the level of TRAF6". FEBS Lett. NETHERLANDS. 442 (2–3): 147–50. doi:10.1016/S0014-5793(98)01645-7. ISSN0014-5793. PMID9928991.
↑Zhang, S Q; Kovalenko A; Cantarella G; Wallach D (March 2000). "Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation". Immunity. UNITED STATES. 12 (3): 301–11. doi:10.1016/S1074-7613(00)80183-1. ISSN1074-7613. PMID10755617.
↑De Valck, D; Jin D Y; Heyninck K; Van de Craen M; Contreras R; Fiers W; Jeang K T; Beyaert R (July 1999). "The zinc finger protein A20 interacts with a novel anti-apoptotic protein which is cleaved by specific caspases". Oncogene. ENGLAND. 18 (29): 4182–90. doi:10.1038/sj.onc.1202787. ISSN0950-9232. PMID10435631.
↑ 8.08.18.2Vincenz, C; Dixit V M (August 1996). "14-3-3 proteins associate with A20 in an isoform-specific manner and function both as chaperone and adapter molecules". J. Biol. Chem. UNITED STATES. 271 (33): 20029–34. doi:10.1074/jbc.271.33.20029. ISSN0021-9258. PMID8702721.
↑ 9.09.1De Valck, D; Heyninck K; Van Criekinge W; Vandenabeele P; Fiers W; Beyaert R (September 1997). "A20 inhibits NF-kappaB activation independently of binding to 14-3-3 proteins". Biochem. Biophys. Res. Commun. UNITED STATES. 238 (2): 590–4. doi:10.1006/bbrc.1997.7343. ISSN0006-291X. PMID9299557.
↑Zheng C, Huang Y, Ye Z, Wang Y, Tang Z, Lu J, Wu J, Zhou Y, Wang L, Huang Z, Yang H, Xue A (2018) Infantile onset intractable inflammatory bowel disease due to novel heterozygous mutations in TNFAIP3 (A20). Inflamm Bowel Dis doi: 10.1093/ibd/izy165
Further reading
Dixit VM, Green S, Sarma V, et al. (1990). "Tumor necrosis factor-alpha induction of novel gene products in human endothelial cells including a macrophage-specific chemotaxin". J. Biol. Chem. 265 (5): 2973–8. PMID2406243.
Cooper JT, Stroka DM, Brostjan C, et al. (1996). "A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism". J. Biol. Chem. 271 (30): 18068–73. doi:10.1074/jbc.271.30.18068. PMID8663499.
Vincenz C, Dixit VM (1996). "14-3-3 proteins associate with A20 in an isoform-specific manner and function both as chaperone and adapter molecules". J. Biol. Chem. 271 (33): 20029–34. doi:10.1074/jbc.271.33.20029. PMID8702721.
De Valck D, Heyninck K, Van Criekinge W, et al. (1996). "A20, an inhibitor of cell death, self-associates by its zinc finger domain". FEBS Lett. 384 (1): 61–4. doi:10.1016/0014-5793(96)00283-9. PMID8797804.
De Valck D, Heyninck K, Van Criekinge W, et al. (1997). "A20 inhibits NF-kappaB activation independently of binding to 14-3-3 proteins". Biochem. Biophys. Res. Commun. 238 (2): 590–4. doi:10.1006/bbrc.1997.7343. PMID9299557.
Heyninck K, Beyaert R (1999). "The cytokine-inducible zinc finger protein A20 inhibits IL-1-induced NF-kappaB activation at the level of TRAF6". FEBS Lett. 442 (2–3): 147–50. doi:10.1016/S0014-5793(98)01645-7. PMID9928991.
De Valck D, Jin DY, Heyninck K, et al. (1999). "The zinc finger protein A20 interacts with a novel anti-apoptotic protein which is cleaved by specific caspases". Oncogene. 18 (29): 4182–90. doi:10.1038/sj.onc.1202787. PMID10435631.
Zhang SQ, Kovalenko A, Cantarella G, Wallach D (2000). "Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation". Immunity. 12 (3): 301–11. doi:10.1016/S1074-7613(00)80183-1. PMID10755617.
Klinkenberg M, Van Huffel S, Heyninck K, Beyaert R (2001). "Functional redundancy of the zinc fingers of A20 for inhibition of NF-kappaB activation and protein-protein interactions". FEBS Lett. 498 (1): 93–7. doi:10.1016/S0014-5793(01)02504-2. PMID11389905.
Van Huffel S, Delaei F, Heyninck K, et al. (2001). "Identification of a novel A20-binding inhibitor of nuclear factor-kappa B activation termed ABIN-2". J. Biol. Chem. 276 (32): 30216–23. doi:10.1074/jbc.M100048200. PMID11390377.
Baltathakis I, Alcantara O, Boldt DH (2001). "Expression of different NF-kappaB pathway genes in dendritic cells (DCs) or macrophages assessed by gene expression profiling". J. Cell. Biochem. 83 (2): 281–90. doi:10.1002/jcb.1231. PMID11573245.
Zetoune FS, Murthy AR, Shao Z, et al. (2002). "A20 inhibits NF-kappa B activation downstream of multiple Map3 kinases and interacts with the I kappa B signalosome". Cytokine. 15 (6): 282–98. doi:10.1006/cyto.2001.0921. PMID11594795.
Wu WS, Xu ZX, Chang KS (2002). "The promyelocytic leukemia protein represses A20-mediated transcription". J. Biol. Chem. 277 (35): 31734–9. doi:10.1074/jbc.M201648200. PMID12080044.