Fas (death receptor) signaling pathway and its inhibition

Fas (death receptor) signaling pathway and its inhibition. Fas (or other death receptor) signaling is triggered on target cells by receptor tri(multi)merization subsequent to FasL (or other appropriate trimeric death ligand). Subsequent recruitment of FADD (by DD–DD interaction) and procaspase-8 or -10 (by DED–DED interaction) leads to upstream caspase (caspase-8 or -10) autoactivation, which initiates apoptosis by subsequent cleavage of downstream effector caspases (caspase-3, -6, and -7). Death receptor apoptosis can be inhibited at different points (red): at the receptor level, e.g., by soluble ligands (a) and/or decoy receptors; (b) by receptor internalization, e.g., by adenovirus E3-10.4/14.5K (c); by downregulation of receptor expression, e.g., by oncogenic H-Ras (c); during signal transduction by FLIPs (d, e, and f); and at the effector stage (by caspase inhibitors, e.g., cowpox-encoded CrmA, baculovirus p35, adenovirus 14.7, and/or IAPs [g]).

Publication

Inhibition of Death Receptor Signaling by Flice-Inhibitory Protein as a Mechanism for Immune Escape of Tumors. (1999) Lars E. French, et al. J Exp Med. 1999 Oct 4;190(7):891-894. Figure: F1. All organisms Homo sapiens Drosophila melanogaster

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