부산대학교 도서관

The binding of heterotrimeric lymphotoxin, LTα 1 β 2 , to the LTβ receptor (LTβ R), a member of the tumor necrosis factor receptor (TNFR) superfamily, induces nuclear factor κ B (NF-κ B) activation and cell death in HT29 adenocarcinoma cells. We now show that treatment with LTα 1 β 2 or agonistic LTβ R antibodies causes rapid recruitment of TNFR-associated factor 3 (TRAF3) to the LTβ R cytoplasmic domain. Further, stable overexpression of a TRAF3 mutant that lacks the RING and zinc finger domains inhibits LTβ R-mediated cell death. The inhibition is specific for LTβ R cell death signaling, since NF-κ B activation by LTα 1 β 2 and Fasmediated apoptosis are not inhibited in the same cells. The mutant and endogenous TRAF3s are both recruited at equimolar amounts to the LTβ R, suggesting that the mutant disrupts the function of the signaling complex. These results implicate TRAF3 as a critical component of the LTβ R death signaling complex and indicate that at least two independent signaling pathways are initiated by LTβ R ligation.