TNFAIP3
TNFAIP3종양괴사인자 알파유도단백질3 또는 A20은 TNFAIP3유전자에 [5][6]의해 인체 내에서 암호화되는 단백질이다.
이 유전자는 종양괴사인자(TNF)에 의해 발현이 빠르게 유도되는 유전자로 확인됐다.이 유전자에 의해 코드된 단백질은 아연 핑거 단백질과 탈유화 효소이며, TNF 매개 아포토시스뿐만 아니라 NF-카파 B 활성화를 억제하는 것으로 나타났다.A20 단백질은 고대 단백질로, 단백질 상동물은 보존된 단백질 도메인 조성을 가진 cnidaria(산호, 해파리, 아네몬)까지 발견될 수 있습니다.[7] TNFAIP3의 녹아웃 마우스 모델과 전사 억제제(KCHIP3)를 사용하여 TNFAIP3는 엔도톡신 및 TNF 유도 NF-카파 B 반응을 [8][9][10]종료함으로써 염증을 제한하는데 중요한 것으로 나타났다.간단히 말해, TNFAIP3의 디유비퀴티나아제 기능은 내피 아데렌스 [9]접합부에서 VE-카드헤린의 손실을 방지하기 위해 VE-카드헤린에서 유비퀴틴 사슬을 제거하는 것으로 나타났다.
상호 작용
TNFAIP3는 TNIP1,[11] TRAF1,[12][13] TRAF2,[12] IKBKG,[14] TAX1BP1,[15] YWHAB, YWHAB,[16][16][17] YWHAZ[13][18],[16][17] TRAF6 및 YWHA와 상호작용하는 것으로 나타났습니다.
류마티스 관절염과의 관련성
TNFAIP3 궤적은 류마티스 관절염(RA)의 양성 관련 인자와 관련이 있다.rs5029937(T)과 rs6920220(A) SNP는 각각 [19]RA의 위험을 20~40% 증가시킵니다.세 번째 SNP, rs10499194(T)는 류마티스 관절염에서 덜 자주 발견되지만, 이 음성 연관성은 통계적으로 유의미하지 않을 수 있다.
기타 질병
유아기 난치성 염증성 장질환과의 연관성도 [20]보고되었다.
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레퍼런스
- ^ a b c GRCh38: 앙상블 릴리즈 89: ENSG00000118503 - 앙상블, 2017년 5월
- ^ a b c GRCm38: 앙상블 릴리즈 89: ENSMUSG000019850 - 앙상블, 2017년 5월
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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- ^ "Entrez Gene: TNFAIP3 tumor necrosis factor, alpha-induced protein 3".
- ^ Staal J, Driege Y, Haegman M, Borghi A, Hulpiau P, Lievens L, et al. (2018). "Ancient Origin of the CARD-Coiled Coil/Bcl10/MALT1-Like Paracaspase Signaling Complex Indicates Unknown Critical Functions". Frontiers in Immunology. 9: 1136. doi:10.3389/fimmu.2018.01136. PMC 5978004. PMID 29881386.
- ^ Lee EG, Boone DL, Chai S, Libby SL, Chien M, Lodolce JP, Ma A (September 2000). "Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice". Science. 289 (5488): 2350–2354. doi:10.1126/science.289.5488.2350. PMC 3582399. PMID 11009421.
- ^ a b Soni D, Wang DM, Regmi SC, Mittal M, Vogel SM, Schlüter D, Tiruppathi C (May 2018). "Deubiquitinase function of A20 maintains and repairs endothelial barrier after lung vascular injury". Cell Death Discovery. 4 (60): 60. doi:10.1038/s41420-018-0056-3. PMC 5955943. PMID 29796309.
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- ^ a b Song, H Y; Rothe M; Goeddel D V (June 1996). "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. UNITED STATES. 93 (13): 6721–5. Bibcode:1996PNAS...93.6721S. doi:10.1073/pnas.93.13.6721. ISSN 0027-8424. PMC 39093. PMID 8692885.
- ^ a b Heyninck, 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. ISSN 0014-5793. PMID 9928991. S2CID 19072203.
- ^ 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. ISSN 1074-7613. PMID 10755617.
- ^ 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. ISSN 0950-9232. PMID 10435631.
- ^ a b c Vincenz, 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. ISSN 0021-9258. PMID 8702721.
- ^ a b De 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. ISSN 0006-291X. PMID 9299557.
- ^ Evans, P C; Taylor E R; Coadwell J; Heyninck K; Beyaert R; Kilshaw P J (August 2001). "Isolation and characterization of two novel A20-like proteins". Biochem. J. England. 357 (Pt 3): 617–23. doi:10.1042/0264-6021:3570617. ISSN 0264-6021. PMC 1221992. PMID 11463333.
- ^ Stahl EA, Raychaudhuri S, Remmers EF, et al. (June 2010). "Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci". Nat. Genet. 42 (6): 508–14. doi:10.1038/ng.582. PMC 4243840. PMID 20453842.
- ^ 정 C, 황 Y, 예 Z, 왕 Y, 탕 Z, 루 J, 우 J, 저우 Y, 왕 L, 황 Z, 양 H, Xue A(2018) TNFAIPA에서 새로운 헤테로 접합 돌연변이로 인한 난치성 염증성 대장 질환 발병.염증 대장 디도이: 10.1093/ibd/이지165
추가 정보
- 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. doi:10.1016/S0021-9258(19)39896-5. PMID 2406243.
- 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. PMID 8663499.
- Meng Z, Zhao T, Zhou K, et al. (2017). "A20 Ameliorates Intracerebral Hemorrhage-Induced Inflammatory Injury by Regulating TRAF6 Polyubiquitination". J. Immunol. 198 (2): 820–31. doi:10.4049/jimmunol.1600334. PMC 5220121. PMID 27986908.
- Song HY, Rothe M, Goeddel DV (1996). "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. 93 (13): 6721–5. Bibcode:1996PNAS...93.6721S. doi:10.1073/pnas.93.13.6721. PMC 39093. PMID 8692885.
- 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. PMID 8702721.
- 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. PMID 8797804. S2CID 29040964.
- 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. PMID 9299557.
- Eliopoulos AG, Blake SM, Floettmann JE, et al. (1999). "Epstein-Barr virus-encoded latent membrane protein 1 activates the JNK pathway through its extreme C terminus via a mechanism involving TRADD and TRAF2". J. Virol. 73 (2): 1023–35. doi:10.1128/JVI.73.2.1023-1035.1999. PMC 103922. PMID 9882303.
- 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. PMID 9928991. S2CID 19072203.
- Heyninck K, De Valck D, Vanden Berghe W, et al. (1999). "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. 145 (7): 1471–82. doi:10.1083/jcb.145.7.1471. hdl:1854/LU-113881. PMC 2133159. PMID 10385526.
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- 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. PMID 10755617.
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- 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. PMID 11389905. S2CID 32414520.
- 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. PMID 11390377.
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