Expression level of c-FLIP versus Fas determines susceptibility to Fas ligand-induced cell death in murine thymoma EL-4 cells.
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.
Kataoka
Takao
T
Department of Bioengineering, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan. tkataoka@bio.titech.ac.jp
Ito
Mika
M
Budd
Ralph C
RC
Tschopp
Jürg
J
Nagai
Kazuo
K
D000818:Animals; D017209:Apoptosis; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002166:Camptothecin / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics*; D061945:Caspase Inhibitors; D002462:Cell Membrane / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D015536:Down-Regulation; D004317:Doxorubicin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D053222:Fas Ligand Protein; D015870:Gene Expression; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D016685:Mitomycin / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013945:Thymoma; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism*
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins; D061945:Caspase Inhibitors; C506387:Cflar protein, mouse; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D011500:Protein Synthesis Inhibitors; D019014:fas Receptor; D016685:Mitomycin; D005047:Etoposide; D004317:Doxorubicin; D003513:Cycloheximide; D002166:Camptothecin