A transmembrane protein (Fas antigen, Fas receptor, TNFRSF6, 319 aa) of the tumour necrosis factor receptor superfamily (see tumour necrosis factor receptors) with homology to the nerve growth factor receptor that is important in negative selection of autoreactive T-cells in the thymus. Fas-associated factor 1 (FAF-1, 650 aa) is involved in negative regulation of NFκB activation probably both by interacting with the pyrin domains of several PYPAFs and by suppressing IκB kinase (IKK) activation by interacting with IKKβ and blocking assembly of the IKK complex, in response to proinflammatory stimuli (e.g. TNFα, IL-1β, LPS). Fas-associated via death domain (FADD, Mort1, 208 aa) is an adaptor protein that mediates signalling from all known death domain-containing members of the TNF receptor superfamily death receptors to caspases involved in apoptotic cell death. The 11q13.3 region where FADD is located is amplified in several human malignancies. Fas ligand (FasL) is a type II transmembrane protein (281 aa), similar to tumour necrosis factor, expressed on activated splenocytes and thymocytes. Fas ligand has three binding sites for Fas and thus stimulates trimer formation; subsequent intracellular signalling leads to apoptotic death of the FasR-bearing cell. The metalloprotease ADAM10 will cleave FasL in T cells to produce an N-terminal fragment without the receptor-binding extracellular domain. This FasL fragment is further processed by a signal peptide peptidase-like enzyme (SPPL2a) that liberates a small unstable fragment mainly containing the intracellular FasL domain which translocates to the nucleus and will inhibit transcription.
Subjects: Medicine and Health — Chemistry.