title: The CD95 (APO-1/Fas) receptor activates NF-kappaB independently of its cytotoxic function.
abstract: 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-kappaB 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-kappaB 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-kappaB activation. Taken together, these observations indicate that CD95 has a function that involves activation of NF-kappaB and that appears to be unrelated to its role as an inducer of apoptotic cell death.
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: A
authors.initials: A
authors.lastname: Ponton
authors.forename: M V
authors.initials: MV
authors.lastname: Clément
authors.forename: I
authors.initials: I
authors.lastname: Stamenkovic
mesh_terms: D017209:Apoptosis; D001483:Base Sequence; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011993:Recombinant Fusion Proteins; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D011993:Recombinant Fusion Proteins; D019014:fas Receptor