Inhibition of fas death signals by FLIPs.
The death receptor Fas is a member of the tumor necrosis factor receptor family; upon interaction with its ligand it efficiently activates caspases and induces apoptosis. Despite abundant Fas surface expression, however, Fas death-signals are frequently interrupted. Many viruses express antiapoptotic proteins, including caspase inhibitors, Bcl-2 homologues and death-effector-domain-containing proteins that are termed FLIPs (FLICE [Fas-associated death-domain-like IL-1beta-converting enzyme]-inhibitory proteins). Cellular homologues of these inhibitors have been identified. Cellular FLIPs structurally resemble caspase-8 except that they lack proteolytic activity. FLIPs are highly expressed in tumor cells, T lymphocytes and healthy, but not injured, myocytes; this suggests a critical role of FLIPs as endogenous modulators of apoptosis.
Tschopp
J
J
Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH-1066, Epalinges, Switzerland. jurg.tschopp@ib.unil.ch
Irmler
M
M
Thome
M
M
D000818:Animals; D017209:Apoptosis; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000502:physiology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000502:physiology; D053222:Fas Ligand Protein; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D019014:fas Receptor / Q000502:physiology*
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; D061945:Caspase Inhibitors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D020169:Caspases