Toso, a cell surface, specific regulator of Fas-induced apoptosis in T cells

Fas is a surface receptor that can transmit signals for Apoptosis. Using retroviral cDNA library-based functional cloning we identified a gene, toso, that blocks Fas-mediated Apoptosis. Toso expression was confined to lymphoid cells and was enhanced after cell-specific activation processes in T cells. Toso appeared limited to inhibition of Apoptosis mediated by members of the TNF Receptor family and was capable of inhibiting T cell self-killing induced by TCR activation processes that up-regulate Fas ligand. We mapped the effect of Toso to inhibition of Caspase-8 processing, the most upstream Caspase activity in Fas-mediated signaling, potentially through activation of cFLIP. Toso therefore serves as a novel regulator of Fas-mediated Apoptosis and may act as a regulator of cell fate in T cells and other hematopoietic lineages.