Abstract
The signaling adapter protein tumor necrosis factor receptor (TNFR)-associated factor 3 (TRAF3) is both modified by and contributes to several types of ubiquitination events. TRAF3 plays a variety of context-dependent regulatory roles in all types of immune cells. In B lymphocytes, TRAF3 contributes to regulation of signaling by members of both the TNFR superfamily and innate immune receptors. TRAF3 also plays a unique cell type-specific and critical role in the restraint of B-cell homeostatic survival, a role with important implications for both B-cell differentiation and the pathogenesis of B-cell malignancies. This review focuses upon the relationship between ubiquitin and TRAF3, and how this contributes to multiple functions of TRAF3 in the regulation of signal transduction, transcriptional activation, and effector functions of B lymphocytes.