Controlling TRAIL-mediated caspase-3 activation

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• executioner caspases, such as caspase-3, -6 or –7, were activated by proteolytic cleavage by initiator caspases such as caspase-2, -8, -9 or –10

• active dimer fragments capable in turn to process various substrates as the PARP (Poly-ADP-Ribose-Polymerase)

• dimerization alone was sufficient to induce initiator caspase activation

• full p20 caspase-3 fragment processing is required for TRAIL-mediated apoptosis execution in a Bax-dependent fashion

• IAPs, have been shown to bind to and inhibit caspases downstream mitochondria.

• XIAP inhibits caspase-3 via its BIR2 domain

• exogenous cytochrome c enabled caspase-3 activation

• Smac-induced cytochrome c release has been shown to be independent of Bax in human carcinoma cells