THE CD95 (APO-1 FAS) RECEPTOR ACTIVATES NF-KAPPA-B INDEPENDENTLY OF ITS CYTOTOXIC FUNCTION/

Engagement of the CD95 (APO-1/Fas) receptor induces apoptosis in a var iety of cell types, However, the nature of the cytotoxic signal and th e intermediate messenger molecules remain to be elucidated, In an effo rt to understand CD95-mediated signaling, we assessed possible changes in the DNA binding activity of NF-kappa B as a result of CD95 engagem ent in various tumor cells, By performing electrophoresis mobility shi ft assays, we show that CD95 can stimulate the DNA binding activity of NF-kappa B in a variety of cells, irrespective of their sensitivity o r resistance to CD95-mediated cytotoxicity, Moreover, deletion of 37 c arboxyl-terminal residues from the cytoplasmic domain of CD95, which a brogates CD95-mediated apoptosis, only marginally affects NF-kappa KB activation. Taken together, these observations indicate that CD95 has a function that involves activation of NF-kappa B and that appears to be unrelated to its role as an inducer of apoptotic cell death.