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. Author manuscript; available in PMC: 2009 Dec 15.
Published in final edited form as: Biochem Pharmacol. 2008 Sep 17;76(12):1694–1704. doi: 10.1016/j.bcp.2008.09.007

Fig. 9. Proposed signaling pathway of c-FLIP siRNA-triggered spontaneous apoptosis in MCF-7 cells.

Fig. 9

In this signaling pathway, we propose that an apoptotic inhibitory complex (AIC) comprised of DR5, FADD, caspase-8, and c-FLIPL exists, and c-FLIPL inhibits caspase-8 activation. The knockdown of c-FLIPL using a c-FLIP-specific siRNA induces DISC activation by triggering DR5- and FADD-mediated activation of procaspase-8, forming active caspase-8. Active caspase-8 cleaves Bid to form tBid, leading to the release of cytochrome c from the mitochondria. Mitochondrial cytochrome c release activates procaspase-9 producing active caspase-9, which activates downstream caspases-6 and -7 thereby inducing apoptosis. The solid lines indicate protein binding partners and the brackets show protein complexes that comprise the AIC and DISC.