Cleavage of translation initiation factor 4G (eIF4G) during anti-Fas IgM-induced apoptosis does not require signalling through the p38 mitogen-activated protein (MAP) kinase.
Initiation factor (eIF) 4G plays a key role in the regulation of translation, acting as a bridge between eIF4E and eIF3, to allow an mRNA molecule to associate with the 40S ribosomal subunit. In this study, we show that activation of the Fas/CD95 receptor complex in Jurkat cells induces the degradation of eIF4G, the inhibition of total protein synthesis and cell death. These responses were prevented by the caspase inhibitors, zVAD.FMK and zDEVD.FMK. We also show that, in contrast to Saccharomyces cerevisiae, although rapamycin caused a modest inhibition of protein synthesis it did not induce apoptosis or the cleavage of eIF4G. Studies with the specific inhibitor, SB203580, have shown that signalling through the p38 MAP kinase pathway is not required for either the Fas/CD95-induced cleavage of eIF4G or cell death. These data suggest that the cleavage of eIF4G and the inhibition of translation play an integral role in Fas/CD95-induced cell death in Jurkat cells.
Morley
S J
SJ
Biochemistry Laboratory, School of Biological Sciences, University of Sussex, Falmer, Brighton, UK. s.j.morley@sussex.ac.uk
McKendrick
L
L
Bushell
M
M
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D018053:Arsenites / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D061945:Caspase Inhibitors; D002470:Cell Survival / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology; D039561:Eukaryotic Initiation Factor-4E; D039603:Eukaryotic Initiation Factor-4G; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007075:Immunoglobulin M; D019169:Jurkat Cells; D020928:Mitogen-Activated Protein Kinases; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010766:Phosphorylation; D039102:Poly(A)-Binding Proteins; D014176:Protein Biosynthesis / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000378:metabolism; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D019014:fas Receptor / Q000276:immunology / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases
D000590:Amino Acid Chloromethyl Ketones; D018053:Arsenites; D061945:Caspase Inhibitors; D039561:Eukaryotic Initiation Factor-4E; D039603:Eukaryotic Initiation Factor-4G; D007093:Imidazoles; D007075:Immunoglobulin M; D010448:Peptide Initiation Factors; D039102:Poly(A)-Binding Proteins; D011725:Pyridines; D016601:RNA-Binding Proteins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D019014:fas Receptor; D005047:Etoposide; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C015001:arsenite; C093642:SB 203580; D020123:Sirolimus