Figure 3
The extrinsic apoptosis pathway. (a) Fas and DR4/5 are activated by the binding of their respective ligands FasL and TRAIL; the receptors then bind to FADD via the death domain (DD). Then, the death effector domain (DED) of FADD binds to procaspase-8/10, forming the death-inducing signalling complex (DISC) to facilitate the autoproteolytic cleavage of procaspase-8/10, which induces the activation of the caspase cascade and ultimately results in apoptosis. (b) In particular cells, activated caspase-8 cleaves the pro-apoptotic protein Bid to create truncated Bid (tBid), and this results in the activation of the mitochondria-mediated apoptotic signalling pathway. (c) TNFR1, EDAR and DR3/6 are activated by the binding of their respective ligands. TNFR1 recruits TRADD, an adaptor protein that binds to TNF receptor-associated factors (TRAFs), receptor-interacting protein kinase (RIP1) and cellular inhibitor of apoptosis (cIAPs), forming the initial membrane pro-survival complex (complex I), which stimulates the MAPK/JNK and NF-κB pathways to facilitate cell survival or apoptosis. (d) Complex I forms two types of cytoplasmic apoptotic complexes, TRADD-dependent complex IIA and RIP1-dependent complex IIB, which activate caspase-8, thus initiating apoptosis (some inspiration came from these articles47, 48, 49, 50, 51, 52)
