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FAS ligand

abbr. FASL; FASLG (approved gene symbol) (CD95 ligand (abbr. CD95L); also APO-1 ligand or APTL [Apoptosis antigen ligand]). Based on homology with other members of the TNF ligand protein superfamily the protein is referred to also as TNF ligand superfamily member 6 [TNFSF6]. In the nomenclature of CD antigens this protein has been given the designation CD178.

The ligand binding to the FAS antigen (see: APO-1) has been purified from a cell line of cytotoxic rat T-lymphocytes as a membrane glycoprotein of 40 kDa.

FAS ligand is a membrane-bound protein of 31 kDa (278 amino acids) that belongs to the protein family related to TNF, which also includes ligands for CD27 (CD27 ligand), CD30 (CD30 ligand), and CD40 (CD40 ligand).

Overexpression of the FAS ligand on the cell surface has been shown to cause shedding of the protein, and the soluble form of the FAS ligand can actively trigger apoptosis by binding to FAS.

The gene encoding the murine FAS ligand has been localized to the gld region of mouse chromosome 1. Mice homozygous for gld (generalized lymphoproliferative disease) are characterized by abnormal T-cell populations in the spleen and lymph nodes and suffer from autoimmune disease-like systemic lupus erythematosus. The FAS ligand from gld mice has been shown to carry a point mutation in the C-terminal region. gld-derived FAS ligand cannot induce cell death by apoptosis in cells expressing the FAS antigen (see also: lpr; lymphoproliferative disease).

For a factor that acts physiologically to limit apoptosis induced by FAS ligand see: FAS-beta.

The functional activity of FAS ligand on Th1 cells has been shown to be augmented by IGIF.

It has been suggested by Bellgrau et al (1995) that the expression of a functional FAS ligand by Sertoli cells may be responsible for the immune-privileged nature of testis. This suggestion is based on experiments showing that testis tissue derived from mutant gld mice that had been transplanted under the kidney capsule of allogenic mice is rejected whereas testis grafts from mice expressing functional FAS ligand can survive indefinitely under these circumstances.

A study by Stuart et al (1997) has suggested a correlation between high levels of FAS ligand expression in the cornea and successful corneal transplantation.

For other entries pertaining to cell death mechanisms see also the Apoptosis Dictionary section of this encyclopedia.

LAST MODIFIED: 15/03/1999

See REFERENCES for entry FAS ligand

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