Signaling pathways to apoptosis
Apoptosis is activated through two major signaling pathways — the 'intrinsic' and the 'extrinsic' pathways.1,2 The intrinsic pathway is triggered from within the cell by developmental cues or severe cell stress, such as DNA damage. The extrinsic pathway is activated when a pro-apoptotic ligand, such as endogenous Apo2L/TRAIL (apoptosis-inducing ligand 2/tumor necrosis factor-related apoptosis-inducing ligand), binds to pro-apoptotic receptors, such as DR4 and DR5.
The extrinsic and intrinsic pathways converge via activation of intracellular enzymes called 'caspases' (Figure 2.1).3,4 The caspase cascade ultimately triggers cell death through the destruction of cellular proteins, which are important for cell viability.
Figure 2.1. Intrinsic and extrinsic pathway signaling for apoptosis.Click here to view a PDF of this image.
Adapted from Ashkenazi 2002. Reproduced with permission from Nature Reviews Cancer.