(a) Death-Receptor signaling (left) is triggered by members of the death receptor superfamily (FasL, TNF). Binding of FasL to Fas induces receptor clustering and formation of the Death-Inducing Signaling Complex (DISC). This complex recruits and activates caspase-8. Active caspase-8 can induce apoptosis through direct cleavage of caspase -3, -7 or through the cleavage of Bid and subsequent triggering of the mitochondrial-mediated pathway.
(b) Classical Granzyme B/perforin-mediated pathway. Granzyme B delivery into the cytoplasm is facilitated by the pore-forming protein perforin. Once in the cytoplasm, GrB initiates apoptosis through the cleavage of Bid, which in turns triggers cytochrome c release, apoptosome formation, and caspase -3, -7 activation. Granzyme B can also bypass the mitochondrial-mediated pathway and initiate caspase activation directly and/or may cleave caspase substrates.
