Blood, Vol. 94 No. 10 (November 15), 1999:
pp. 3456-3467
Cloning and Expression of a Short Fas Ligand: A New Alternatively
Spliced Product of the Mouse Fas Ligand Gene
Emira Ayroldi,
Francesca D'Adamio,
Ornella Zollo,
Massimiliano Agostini,
Rosalba Moraca,
Lorenza Cannarile,
Graziella Migliorati,
Domenico V. Delfino, and
Carlo Riccardi
From the Department of Clinical and Experimental Medicine, Section of
Pharmacology, Perugia University Medical School, Perugia, Italy.
The Fas/FasL system mediates apoptosis in several different cell
types, including T lymphocytes. Fas ligand (FasL), a 40-kD type II
membrane protein also expressed in activated T cells, belongs to the
tumor necrosis factor ligand family. We describe a new alternative
splicing of mouse FasL, named FasL short (FasLs), cloned by reverse
transcriptase-polymerase chain reaction. FasLs is encoded by part of
exon 1 and part of exon 4 of FasL gene. The protein encoded by FasLs
mRNA has a putative initiation code at position 756 and preserves the
same reading frame as FasL, resulting in a short molecule lacking the
intracellular, the transmembrane, and part of the extracellular
domains. RNase protection and immunoprecipitation analysis showed that
FasLs is expressed in nonactivated normal spleen cells and in hybridoma
T cells and that it is upregulated upon activation by anti-CD3
monoclonal antibody (MoAb). Moreover, FasLs-transfected cells expressed
soluble FasLs in the supernatant and became resistant to apoptosis
induced by agonist anti-Fas MoAb. Thus, FasLs, a new alternative
splicing of FasL, is involved in the regulation of Fas/FasL-mediated
cell death.
