Tumor necrosis factor receptor-associated factors (TRAFs)

Tumor necrosis factor receptor-associated factors (TRAFS) were initially di scovered as adaptor proteins that couple the tumor necrosis factor receptor family to signaling pathways. More recently they have also been shown to b e signal transducers of Toll/interleukin-l family members. Six members of t he TRAF family have been identified. All TRAF proteins share a C-terminal h omology region termed the TRAF domain that is capable of binding to the cyt oplasmic domain of receptors, and to other TRAF proteins. In addition, TRAF s 2-6 have RING and zinc finger motifs that are important for signaling dow nstream events. TRAF proteins are thought to be important regulators of cel l death and cellular responses to stress, and TRAF2, TRAF5 and TRAF6 have b een demonstrated to mediate activation of NF-kappaB and JNK. TRAF proteins are expressed in normal and diseased tissue in a regulated fashion, suggest ing that they play an important role in physiological and pathological proc esses.