Targeting BCL2-Proteins for the Treatment of Solid Tumours

Figure 1

Apoptotic signalling pathways. In the extrinsic pathway, apoptosis can be initiated at the cell surface by ligation of death receptors. This results in the activation of caspase-8 at the death inducing signalling complex (DISC) and, in some circumstances, cleavage of the BH3-only protein BID. In the intrinsic pathway, apoptosis is initiated at the mitochondria and is regulated by BCL2-proteins. Activation of the intrinsic pathway, for example, by cellular stress, results in loss of mitochondrial membrane potential, release of cytochrome c, and activation of caspase-9 in the Apaf-1 containing apoptosome. Both pathways converge into the activation of the executioner caspases, for example, caspase-3. Caspases may be inhibited by the Inhibitor of apoptosis proteins (IAPs).