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Fas Signaling Pathway. SIGMA-ALDRICH. Fas Signaling Pathway
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Fas Signaling Pathway SIGMA-ALDRICH
Fas Signaling Pathway Fas/APO-1/CD95 (36 kDa) is a member of the tumor necrosis factor (TNF) receptor superfamily, a family of transmembrane receptors that also includes the p75 neurotrophin receptor, TNF-R1, and a variety of other cell surface receptors. Fas has been shown to be an important mediator of apoptotic cell death, as well as being involved in inflammation. Binding of the Fas ligand (Fas-L) induces trimerization of Fas in the target cell membrane. Activation of Fas causes the recruitment of Fas-associated protein with death domain (FADD) via interactions between the death domains of Fas and FADD. Procaspase 8 binds to Fas-bound FADD via interactions between the death effector domains (DED) of FADD and pro-caspase 8 leading to the activation of caspase 8. Activated caspase 8 cleaves (activates) other procaspases, in effect beginning a caspase cascade that ultimately leads to apoptosis. Caspases cleave nuclear lamins, causing the nucleus to break down and lose its normal structure. Fas-induced apoptosis can be effectively blocked at several stages by either FLICE-inhibitory protein (FLIP), by Bcl-2, or by the cytokine response modifier A (CrmA). References Juo, P., et al., FADD is required for multiple signaling events downstream of the receptor Fas. Cell Growth Differ., 10, 797-804 (1999). Huang, D.C., et al., Activation of Fas by FasL induces apoptosis by a mechanism that cannot be blocked by Bcl-2 or Bcl-XL . Proc. Natl. Acad. Sci. USA., 96, 14871-14876 (1999). Wang, J., et al., Inhibition of Fas-mediated apoptosis by the B cell antigen receptor through c-FLIP. Eur. J. Immunol., 30, 155-163 (2000).