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

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