Intra- and interdimeric caspase-8 self-cleavage controls strength and timing of CD95-induced apoptosis.

ABSTRACT: Apoptosis in response to the ligand CD95L (also known as Fas ligand) is initiated by caspase-8, which is activated by dimerization and self-cleavage at death-inducing signaling complexes (DISCs). Previous work indicated that the degree of substrate cleavage by caspase-8 determines whether a cell dies or survives in response to a death stimulus. To determine how a death ligand stimulus is effectively translated into caspase-8 activity, we assessed this activity over time in single cells with compartmentalized probes that are cleaved by caspase-8 and used multiscale modeling to simultaneously describe single-cell and population data with an ensemble of single-cell models. We derived and experimentally validated a minimal model in which cleavage of caspase-8 in the enzymatic domain occurs in

SUBMITTER: Kallenberger SM 

PROVIDER: S-EPMC4208692 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature