TRAF5, AN ACTIVATOR OF NF-KAPPA-B AND PUTATIVE SIGNAL TRANSDUCER FOR THE LYMPHOTOXIN-BETA RECEPTOR

Tumor necrosis factor (TNF) receptor-associated factors (TRAFs) are si gnal transducers for several members of the TNF receptor superfamily. We have identified a novel member of the TRAF family by degenerate oli gonucleotide polymerase chain reaction amplification that contains a z inc RING finger and zinc finger motifs, a coiled-coil region, and a C- terminal ''TRAF'' homology domain. In vitro translated TRAF5 binds to the cytoplasmic region of the lymphotoxin-beta receptor (LT-beta R) bu t not to several other related receptors including CD40, both TNF rece ptors, Fas, and nerve growth factor receptor. TRAF5 and LT-beta R coim munoprecipitate when overexpressed in COS7 cells. TRAF5 mRNA expressio n is found in all visceral organs and overlaps with LT-beta R. These f eatures distinguish TRAF5 from the other members of the TRAF family. T he transcription factor NF-kappa B is activated in HEK293 cells by ove rexpression of full length TRAF5 but not a truncated form lacking the zinc binding region, Furthermore, overexpression of LT-beta R in HEK29 3 cells also results in activation of NF-kappa B, which is partially i nhibited by the truncated TRAF5 mutant. These results show TRAF5 is fu nctionally similar to TRAF2 in that both mediate activation NF-kappa B and implicate TRAF5 as a signal transducer for LT-beta R.