The Death Receptor Pathway

The death receptor pathway is activated when death receptors such as members of the tumour necrosis factor (TNF) family are stimulated by specific death ligands. This recruits adapter proteins that activate initiator caspases , which in turn activate effector caspases such as caspase 3. The mitochondrial pathway is activated by diverse signals, one being DNA damage. In the presence of DNA damage that cannot be repaired, the p53 protein activates a subpathway that results in release of cytochrome c from the mitochondrion, with subsequent involvement of the apoptosome and activation of an initiator caspase, caspase 9. The apoptosome is a complex of procaspase 9, cytochrome c and apoptotic-activating protease factor-1 (Apaf-1). Both these pathways converge on the effector caspase (e.g. caspase 3), which brings about the demise of the cell. The survival factor subpathway (shown here faded) normally holds apoptosis at bay by inhibiting the mitochondrion pathway through activation of the antiapoptotic factor Bcl-2. The receptor labelled 'R' represents the respective receptors for trophic factors, growth factors, cell-to-cell contact factors (adhesion molecules, integrins), etc. Continuous stimulation of these receptors is necessary for cell survival/proliferation. If this pathway is non-functional , this antiapoptotic drive is withdrawn. IAP, inhibitor of apoptosis.