Abstract
The caspase-8 inhibitor c-FLIP blocks death receptor-mediated cell death and plays an essential role in the regulation of lymphocyte homeostasis and the immune escape of tumors. The murine thymoma cell line EL-4 was resistant to Fas ligand (FasL)-induced apoptosis by constitutive expression of FLIP (L). Cycloheximide downregulated the expression of FLIP (L) and markedly sensitized EL-4 cells to FasL-induced apoptosis. In contrast, DNA-damaging agents sensitized EL-4 cells to FasL-induced cell death via an increase of cell-surface Fas without any influence on FLIP (L) expression. Enforced expression of transfected Fas rendered EL-4 cells highly susceptible to FasL-induced cell death. These findings demonstrate that susceptibility to FasL-induced cell death mainly depends on the expression level of c-FLIP versus cell-surface Fas.
©2002 Elsevier Science (USA).
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis*
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CASP8 and FADD-Like Apoptosis Regulating Protein
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Camptothecin / pharmacology
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Carrier Proteins / genetics*
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Caspase Inhibitors*
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Cell Membrane / metabolism
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Cycloheximide / pharmacology
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Down-Regulation
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Doxorubicin / pharmacology
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Etoposide / pharmacology
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Fas Ligand Protein
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Gene Expression*
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Intracellular Signaling Peptides and Proteins*
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Membrane Glycoproteins / metabolism*
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Mice
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Mitomycin / pharmacology
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Protein Synthesis Inhibitors / pharmacology
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Thymoma
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Transcriptional Activation
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Transfection
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Tumor Cells, Cultured
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Up-Regulation
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fas Receptor / metabolism*
Substances
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CASP8 and FADD-Like Apoptosis Regulating Protein
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Carrier Proteins
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Caspase Inhibitors
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Cflar protein, mouse
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Fas Ligand Protein
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Fasl protein, mouse
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Intracellular Signaling Peptides and Proteins
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Membrane Glycoproteins
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Protein Synthesis Inhibitors
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fas Receptor
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Mitomycin
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Etoposide
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Doxorubicin
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Cycloheximide
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Camptothecin