Fas, also known as APO-1, CD95, and TNFRSF6, was originally identified as a cell-surface protein which binds to monoclonal antibodies that were cytolytic for various human cell lines. In the TNF receptor superfamily nomenclature, Fas is referred to as TNFRSF6. Human and mouse Fas cDNAs encode a 325 and a 327 amino acid residue type 1 membrane protein, respectively, that belongs to the TNF and NGF receptor family. Alternatively spliced cDNAs encoding multiple human Fas isoforms, including a soluble form of Fas lacking the transmembrane domain, have also been identified. Fas is highly expressed in epithelial cells, hepatocytes, activated mature lymphocytes, virus-transformed lymphocytes and other tumor cells. Fas expression has also been detected in mouse thymus, liver, heart, lung, kidney and ovary. The ligand for Fas (FasL) has been identified and shown to be a member of the TNF family of type 2 membrane proteins. FasL is predominantly expressed by activated T-lymphocytes, NK cells, and in tissues with immune-privileged sites. Soluble FasL can be produced by proteolysis of membrane-associated Fas.
Ligation of Fas by FasL or anti-Fas antibody has been shown to induce apoptotic cell death in Fas-bearing cells. Fas plays a role in the down-regulation of the immune reaction and has been shown to be a key mediator of activation-induced death of activated T lymphocytes. Fas-mediated cell death has also been shown to be important for the deletion of activated or autoreactive B lymphocytes. Besides the perforin/granzyme-based mechanism, the Fas system has been identified as the alternate pathway for CTL-mediated cytotoxicity. FasL has also been shown to function in immunological privileged sites by killing infiltrating Fas-bearing lymphocytes and inflammatory cells.
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