Proteomic Profiling of the TRAF3 Interactome Network Reveals a New Role for the ER-to-Golgi Transport Compartments in Innate Immunity

van Zuylen, Wendy J.; Doyon, Priscilla; Clément, Jean-François; Khan, Kashif Aziz; D'Ambrosio, Lisa M.; Dô, Florence; St-Amant-Verret, Myriam; Wissanji, Tasheen; Emery, Gregory; Gingras, Anne-Claude; Meloche, Sylvain; Servant, Marc J.

Tumor Necrosis Factor (TNF) receptor-associated factors (TRAFs) are part of a family of adaptor proteins that bridge the intracellular domains of multiple receptors, such as TNFR, IL1R, and TLRs, to downstream effectors involved in the inflammatory and innate immune signalling pathways. The TRAF family is composed of seven members, TRAF1 through TRAF7. They all share a C-terminal TRAF domain, which is composed of a coiledcoil domain followed by a conserved receptor-interacting domain. This domain mediates self-association and interaction with receptors or signalling proteins. Their N-terminal regions are composed of one or more zinc-finger motifs and, with the exception of TRAF1, a RING-finger domain that mediates E3 ubiquitin ligase activity and signalling [11] . All mammalian TRAFs localize to the cytoplasm except TRAF4, which is found in the nucleus. Importantly, gene deletion studies have identified TRAF3 as a critical mediator involved in the induction of the type I interferons (IFNs) by the RLH pathway [12, 13] .