FAS (CD95)
FAS (CD95) is a death receptor: a cell-surface member of the tumor necrosis factor receptor family whose engagement by its ligand launches the extrinsic apoptosis pathway.
Function
FAS spans the membrane once and carries an intracellular death domain. When FAS ligand (FASL) on a cytotoxic T cell clusters three or more FAS molecules on a target cell, the clustered death domains recruit FADD and procaspase-8 into the death-inducing signaling complex (DISC). Procaspase-8 dimerizes and activates, then cleaves downstream executioner caspases (caspase-3); in type I cells this suffices to kill, and in type II cells the signal must be amplified through the mitochondrial route controlled by the BCL-2 family. The immune system uses FAS to kill infected and transformed cells, and activated lymphocytes use it to delete themselves at the end of a response.
In cancer
Tumors down-regulate FAS, shed it into the serum as a decoy, or express FASL to kill attacking lymphocytes - a reversal sometimes called counterattack. Mutations in the FAS death domain cause autoimmune lymphoproliferative syndrome (ALPS), in which self-reactive lymphocytes accumulate.
Notes
- Human gene symbol: FAS (TNFRSF6, CD95); UniProt P25445; 335 amino acids; TNFR family, death domain.