Figure 2.

Schematic diagram of the major players in the apoptotic pathways. Three signaling pathways in cells can result in apoptosis. Extracellular stress signals activate the death receptors, which leads to the formation of the DISC complex. Caspases-8 and -10 are then activated by the DISC through dimerization. The second pathway is triggered by an intracellular stress stimulus leading to mitochondrial cytochrome c release which is governed by the BCL-2 family proteins. In the cytoplasm, cytochrome c binds to the adaptor protein Apaf-1, which triggers the formation of the caspase-9 activating complex apoptosome. The executioner caspase-3 and -7 are subsequently activated via the proteolytic cleavage by caspase-8 (-10) or caspase-9. The third pathway, which is also triggered by an intracellular signal, results in PIDDosome formation and subsequent activation of the initiator caspase-2. The activation of BID by caspase-2 or caspase-8 (-10) feeds into the BCL-2 family-mediated cytochrome c release.