Figure 9.

TRAIL-induced mutagenesis model. Death receptor ligation promotes formation of the death inducing signalling complex (DISC) and activation of caspase-8, which then activates caspases-3 and/or -7. This can trigger apoptosis (a), through cleavage of numerous cellular substrates including ICAD, whose cleavage provokes activation of CAD which fragments DNA. Data reported herein suggest that in cells bearing only a small number of activated effector caspases, limited caspase-mediated ICAD proteolysis leads to CAD activation and DNA cleavage, but not apoptosis (b). We suggest that inaccurate repair of these lesions creates mutations in surviving cells.