Activation of lymphotoxin-␤ receptor (LT-␤R) by conjugation with heterotrimeric lymphotoxin, LT-␣1/␤2, or by cross-linking with anti-LT-␤R antibodies can trigger apoptosis. We have observed that overexpression of either LT-␤R or the cytoplasmic domain of LT-␤R (LT-␤R(CD)) also induces apoptosis, which may be attributed to the tendency of LT-␤R(CD) to self-associate. The self-association domain of LT-␤R(CD) was mapped to amino acids 324 -377, a region of the protein that is also essential for

more »

... ␤R-induced apoptosis. Furthermore, we have shown that LT-␤R(CD)-induced apoptosis could be inhibited by a TRAF3 dominant negative mutant and by the caspase inhibitors Z-VAD-FMK, DEVD-FMK, and CrmA. The ligand-independent apoptosis induced by LT-␤R(CD) will help us to further dissect LT-␤R signaling pathway.