CUTTING EDGE - APOPTOSIS INDUCED BY A CHIMERIC FAS FLICE RECEPTOR - LACK OF REQUIREMENT FOR FAS-BINDING OR FADD-BINDING PROTEINS/

Current models for Pas (CD95)-mediated apoptosis suggest that FLICE/ca spase-8 is recruited and activated, which results in cell death, Howev er, the role of additional molecules in Pas signaling and FLICE activa tion is not clear, A chimeric Fas/FLICE (F/F) receptor, containing the extracellular/transmembrane portion of Pas and the caspase region of FLICE, mediated anti-Pas apoptosis. FLICE protease subunits were gener ated from the F/F precursor, Killing induced by Fas, but not F/F, was blocked by a dominant negative FADD, Apoptosis triggered through Pas a nd F/F was inhibited by coexpression of CrmA and p35, but not Bcl-xL, F/F bypassed Pas resistance in COS-7 cells and blocking by the death e ffector domain (DED)-containing viral protein MC159. These results sho w that: 1) F/F induces cell death, indicating that FLICE activation is sufficient for apoptosis and dots not require additional Pas-or FADD- binding proteins; and 2) F/F bypasses proximal defects in Pas signalin g that prevent FLICE recruitment or activation.