c-FLIP efficiently rescues TRAF-2-/- cells from TNF-induced apoptosis.
For the past 20 years, it has been known that preparations of Tumor Necrosis Factor alpha (TNF) fail to induce apoptosis due to cytoprotective responses that render cells resistant to its cytotoxic activity. Here we show that TRAF-2-/- embryonic fibroblasts express reduced levels of the anti-apoptotic molecule c-FLIP due to extensive degradation of the protein. Reconstitution of TRAF-2-/- EF with c-FLIP is sufficient for resistance to TNF toxicity. Our results strengthen the role of c-FLIP in protecting cells from the cytotoxic effect of TNF and have implication for the treatment of inflammatory and proliferative disorders.
Guiet
C
C
Basel Institute for Immunology, Grenzacherstrasse 487, Postfach CH-4005, Basel, Switzerland.
Silvestri
E
E
De Smaele
E
E
Franzoso
G
G
Vito
P
P
D000818:Animals; D017209:Apoptosis; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D017353:Gene Deletion; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008858:Microscopy, Phase-Contrast; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011506:Proteins / Q000235:genetics*; D047992:TNF Receptor-Associated Factor 2; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D011506:Proteins; D047992:TNF Receptor-Associated Factor 2; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases