TNF receptor-associated factor 4 (TRAF4) also known as RING finger protein 83 (RNF83) is a protein that in humans is encoded by the TRAF4gene.[1][2][3]
TRAF4 is a member of the TNF receptor associated factor (TRAF) family, a family of scaffold proteins.[4] TRAF proteins connect IL-1R/Toll and TNF receptors with signaling factors that lead to the activation of NF-κB and mitogen-activated protein kinases. However, TRAF4 is not known to interact with TNF receptors and its cellular functions are not well understood.[5]
Protein interactions
TRAF4 has been shown to interact with neurotrophin receptor, p75 (NTR/NTSR1),[6][7] and negatively regulate NTR induced cell death and NF-kappa B activation. This protein has been found to bind to p47phox, a cytosolic regulatory factor included in a multi-protein complex known as NAD(P)H oxidase. This protein thus, is thought to be involved in the oxidative activation of MAPK8/JNK. Alternatively spliced transcript variants have been observed but the full-length nature of only one has been determined.[3]
A recent report indicates that TRAF4 binds to NOD-Like Receptors NOD1 and NOD2, and specifically inhibits activation of NF-κB by the activated NOD2-RIP2 complex [8]
References
↑Regnier CH, Tomasetto C, Moog-Lutz C, Chenard MP, Wendling C, Basset P, Rio MC (Dec 1995). "Presence of a new conserved domain in CART1, a novel member of the tumor necrosis factor receptor-associated protein family, which is expressed in breast carcinoma". J Biol Chem. 270 (43): 25715–21. doi:10.1074/jbc.270.43.25715. PMID7592751.
↑Tomasetto C, Regnier C, Moog-Lutz C, Mattei MG, Chenard MP, Lidereau R, Basset P, Rio MC (Jan 1996). "Identification of four novel human genes amplified and overexpressed in breast carcinoma and localized to the q11-q21.3 region of chromosome 17". Genomics. 28 (3): 367–76. doi:10.1006/geno.1995.1163. PMID7490069.
↑Ye X, Mehlen P, Rabizadeh S, VanArsdale T, Zhang H, Shin H, Wang JJ, Leo E, Zapata J, Hauser CA, Reed JC, Bredesen DE (October 1999). "TRAF family proteins interact with the common neurotrophin receptor and modulate apoptosis induction". J. Biol. Chem. 274 (42): 30202–8. doi:10.1074/jbc.274.42.30202. PMID10514511.
Zapata JM, Pawlowski K, Haas E, et al. (2001). "A diverse family of proteins containing tumor necrosis factor receptor-associated factor domains". J. Biol. Chem. 276 (26): 24242–52. doi:10.1074/jbc.M100354200. PMID11279055.
Xu YC, Wu RF, Gu Y, et al. (2002). "Involvement of TRAF4 in oxidative activation of c-Jun N-terminal kinase". J. Biol. Chem. 277 (31): 28051–7. doi:10.1074/jbc.M202665200. PMID12023963.
Glauner H, Siegmund D, Motejadded H, et al. (2002). "Intracellular localization and transcriptional regulation of tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4)". Eur. J. Biochem. 269 (19): 4819–29. doi:10.1046/j.1432-1033.2002.03180.x. PMID12354113.
Sax JK, El-Deiry WS (2003). "Identification and characterization of the cytoplasmic protein TRAF4 as a p53-regulated proapoptotic gene". J. Biol. Chem. 278 (38): 36435–44. doi:10.1074/jbc.M303191200. PMID12788948.
Fleckenstein DS, Dirks WG, Drexler HG, Quentmeier H (2003). "Tumor necrosis factor receptor-associated factor (TRAF) 4 is a new binding partner for the p70S6 serine/threonine kinase". Leuk. Res. 27 (8): 687–94. doi:10.1016/S0145-2126(02)00325-9. PMID12801526.
Ma BY, Mikolajczak SA, Danesh A, et al. (2005). "The expression and the regulatory role of OX40 and 4-1BB heterodimer in activated human T cells". Blood. 106 (6): 2002–10. doi:10.1182/blood-2004-04-1622. PMID15941918.
Takeshita F, Ishii KJ, Kobiyama K, et al. (2005). "TRAF4 acts as a silencer in TLR-mediated signaling through the association with TRAF6 and TRIF". Eur. J. Immunol. 35 (8): 2477–85. doi:10.1002/eji.200526151. PMID16052631.
Abell AN, Johnson GL (2006). "MEKK4 is an effector of the embryonic TRAF4 for JNK activation". J. Biol. Chem. 280 (43): 35793–6. doi:10.1074/jbc.C500260200. PMID16157600.
