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 If this pathway is non-functional , this antiapoptotic drive is withdrawn.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.
