TRAF3 and its biological function

Tumor necrosis factor receptor associated factor 3 (TRAF3) is one of the most enigmatic members in the TRAF family that consists of six members, TRAF1 to 6. Despite its similarities with other TRAFs in terms of structure and protein-protein association, overexpression of TRAF3 does not induce activation of the commonly known TRAF-inducible signaling pathways, namely NF-kappa B and JNK. This lack of a simple functional assay in combination with the mysterious early lethality of the TRAF3-deficient mice has made the study of the biological function of TRAF3 challenging for almost ten years. Excitingly, TRAF3 has been identified recently to perform two seemingly distinct roles. Namely, TRAF3 functions as a negative regulator of the NF-kappa B pathway and separately, as a positive regulator of type I IFN production, placing itself as a critical regulator of both innate and adaptive immune responses.