Death receptors
(Fas [CD95], TNF receptor 1 [TNFR1], DR4/5): all of these receptors have a homologous intracellular region “death domain.” These death domains bind to adaptor protein (Fas and DR4/5 binds to FADD, TNFR1 to TRADD). These adaptor proteins can activate the cysteine protease, procaspase 8. This can be inhibited by FLIP. The activated caspase 8 activates the executioner caspases (3, 6, and 7), which in turn activate an endonuclease called caspase-activated DNAse as well as others. These endonucleases cleave DNA causing fragmentation and cell death. Caspases also activate proteases that act on actin microfilaments leading to blebbing of the membrane.
