3 FUNCTIONAL SOLUBLE FORMS OF THE HUMAN APOPTOSIS-INDUCING FAS MOLECULE ARE PRODUCED BY ALTERNATIVE SPLICING

Fas/Apo-1 molecule is an apoptosis-signaling cell surface Ag belonging to the TNFR family. To investigate the possibility that soluble forms of the Fas receptor are expressed in human cells, we analyzed Fas mRN A transcripts obtained from activated peripheral mononuclear cells of healthy donors and from human tumor cell lines. We identified and char acterized three human mRNA Fas variants: FasTMDel, FasDel2, and FasDel 3. To determine whether the three transcripts were derived by alternat ive splicing, the Fas genomic intron/exon organization of the regions surrounding the deleted sequences was analyzed in Fas clones isolated from a human genomic library. Expression of the transcripts was studie d in COS cells transiently transfected with the FasTMDel, FasDel2, and FasDel3 cDNAs. Immunocytochemical and in vitro apoptosis inhibition s tudies suggest that the transcripts are expressed as soluble Fas prote ins that may play a functional role in the regulation of apoptosis.