Fas/APO-1/CD95 is
a 36 kDa cell surface type I-membrane glycoprotein with an apparent
molecular weight of 44 kDa on SDSPAGE. Fas is a member of the
tumor necrosis factor receptor (TNFR) family, which includes
TNFR1, TNFR2, CD27, CD30 and CD40. Binding of Fas-ligand (FasL)
to Fas or crosslinking of Fas by anti-Fas monoclonal antibodies
leads to apoptosis of Fas expressing cells. Both Fas and TNFR
contain a 70 amino acids cytoplasmic .death domain. that is responsible
for transmitting signal for apoptosis. Apoptosis induced by Fas-Fas
ligand interaction is inhibited by a number of cytosolic factors
such as the ICE/CED3 family inhibitor CrmA, and the short and
long form of FLIP. Insertion of an early transposable element
in intron 2 of Fas structural gene, as in the mouse lpr mutations,
causes lymphoproliferation and autoimmunity in mutant mice, suggesting
that Fas is involved in clonal deletion of autoreactive T cells.
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