Death receptor mediated (extrinsic) pathway of apoptosis. Schematic representation of signalling through the main death receptors (Fas/CD95, tumour necrosis factor receptor 1 (TNF-R1), tumour necrosis factor related apoptosis inducing ligand receptors 1 and 2 (TRAIL-R1 and TRAIL-R2)). Engagement of death receptors by their cognate ligands results in oligomerisation of the receptor and recruitment of adaptor proteins (Fas associated protein with death domain (FADD), TNF-R1 associated death domain protein (TRADD)), which in turn bind the inactive initiator caspase-8 and/or -10. The resulting complex is referred to as the death inducing signalling complex (DISC). The close proximity of several procaspase molecules results in activation of the caspase by self processing. Active initiator caspases can directly activate downstream caspases such as caspase-3, -6, and -7, or engage the mitochondrial pathway of apoptosis by cleavage and activation of the BH3 only protein Bid (see fig 3 ▶ for details).