Some latest achievements in immunology research

Liu, Wei

Tumor necrosis factor receptor-associated factors (TRAF) were initially discovered as adaptor proteins that couple the tumor necrosis factor receptor (TNFR) family to signaling pathways. More recently they have also been shown to be signal transducers of a large number of receptor families including the TNF receptor family and the Toll-like receptors-interleukin-1 receptors (TLR-IL-1R) family. Wang et al. [17] contributed to a minute review regarding the structure and function of the TRAF family. All the 6 members of the TRAF family share a C-terminal homology region termed the TRAF domain that is capable of binding to the cytoplasmic domain of receptors, and to other TRAF proteins. The 3D structures of the TRAF domain and another N-terminal RING domain are detailedly described in this article. Research studies in the past few years have established the central role of the TRAF proteins in inflammation and immunity by regulating both canonical and noncanonical nuclear factor B (NF-B) pathways as well as type 1 interferons production. Tremendous progresses have been made recently, for instance, the recruitment of TRAF2/5 in a signaling complex mediating the TNF-induced canonical NF-B activation [18] ; the oligomerization of TRAF6 to activate its E3 ubiquitin ligase activity, further leading to transforming growth factor -activated kinase 1 (TAK1) and downstream signal transduction in the TLR-IL-1Rinduced canonical NF-B pathway [19] ; and the degradation of TRAF2 and TRAF3 resulting in the stabilization and accumulation of NF-B-inducing kinase (NIK) in noncanonical NF-B pathway [20, 21] . Notwithstanding, many aspects about the roles played by the TRAF family in NF-B remain unclear and require more investigations.