title: Oligomerization of soluble Fas antigen induces its cytotoxicity.
abstract: Soluble Fas antigen can protect cells against Fas-mediated apoptosis. High level soluble Fas antigen characteristic for blood of patients with autoimmune disease or cancer is believed to prevent the elimination of autoimmune lymphocytes or tumor cells. Here we first report that human recombinant FasDeltaTM, i.e. soluble Fas generated by alternative splicing of the intact exon 6, is capable of inducing death of transformed cells by "reverse" apoptotic signaling via transmembrane Fas ligand. FasDeltaTM, as well as transmembrane Fas antigen, can be either monomeric or oligomeric, and both its forms are efficient in blocking Fas-mediated apoptosis, although the cytotoxic activity is exhibited solely by the latter. An in vivo analysis of soluble Fas antigen showed that unlike in healthy controls, nearly the total FasDeltaTM present in sera of rheumatoid arthritis patients was oligomeric. This resulted in suppression of cell proliferation in the experimental sera and in its promotion in controls. Thus, oligomerization/depolymerization of soluble Fas antigen can regulate its activity and contribute to the pathogenesis of autoimmune diseases and cancer.
authors.affiliation: Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Puschino 142290, Russia.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Proussakova
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Rabaya
authors.forename: Anna B
authors.initials: AB
authors.lastname: Moshnikova
authors.forename: Ekaterina S
authors.initials: ES
authors.lastname: Telegina
authors.forename: Anton
authors.initials: A
authors.lastname: Turanov
authors.forename: Mike G
authors.initials: MG
authors.lastname: Nanazashvili
authors.forename: Igor P
authors.initials: IP
authors.lastname: Beletsky
mesh_terms: D017398:Alternative Splicing; D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000097:blood; D015153:Blotting, Western; D002455:Cell Division; D045744:Cell Line, Tumor; D002850:Chromatography, Gel; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020298:U937 Cells; D019014:fas Receptor / Q000097:blood / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D003432:Cross-Linking Reagents; D018076:DNA, Complementary; D008024:Ligands; D011994:Recombinant Proteins; D019014:fas Receptor; D012313:RNA; D004247:DNA