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

Y Hitoshi, J Lorens, SI Kitada, J Fisher, M LaBarge… - Immunity, 1998 - cell.com
Y Hitoshi, J Lorens, SI Kitada, J Fisher, M LaBarge, HZ Ring, U Francke, JC Reed…
Immunity, 1998cell.com
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 …
Abstract
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.
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