Cell death by apoptosis is a tightly regulated physiological process that enables the elimination of unwanted cells. It is crucial for embryonic development and the maintenance of tissue homeostasis, but also for defense against certain infectious diseases and cancer.
Apoptosis can be triggered from outside the cell, generally after cell–cell contact, by a family of transmembrane proteins called death receptors, which belong to the TNF family of receptors. Six human death receptors (Fas [Apo-1, CD95], TNFR-1, TRAMP [WSL-1/Apo-3/DR-3/LARD], TNF-related apoptosis-inducing ligand [TRAIL]R-1 [DR-4], TRAILR-2 [DR-5, TRICK-2, KILLER], and DR-6) have been identified to date 1,2, and all contain a cytoplasmic sequence named “death domain” (DD) that couples each receptor to caspase cascades essential for the induction of apoptosis. The best studied signaling pathway is the one triggered by binding of Fas ligand (L) to Fas. Schematically,...
