Fig. (3) Overview of apoptotic pathways and viral anti-apoptotic strategies: In the perforin/granzyme pathway (bottom left), effector
caspases are directly activated by granzyme B, which enters the cells with the help of perforin. The death receptor mediated pathway (top
left) is induced by death ligands of the TNF superfamily. Upon receptor engagement the DISC is formed and caspase-8 is activated which
then activates effector caspases such as caspase-3, -6 and -7. The mitochondrial pathway (right) is initiated by various stress signals and
mediated by BH3-only proteins. Once activated, BH3 only proteins inhibit the anti-apoptotic Bcl-2 like proteins, Bak and Bax can then
breach the integrity of the outer mitochondrial membrane and release factors such as cytochrome c from the intermembrane space. Release of
cytochtome c results in apoptosome formation, caspase-9 cleavage and effector caspase activation. The death receptor and the mitochondria
mediated pathways are linked via the BH3 only protein Bid, which is cleaved to tBid by caspase-8 and amplify the extrinsic signal via the
mitochondrion. Anti-apoptotic strategies are indicated in red at the appropriate points within the apoptotic pathway.
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