CLEAVAGE OF TRANSLATION INITIATION-FACTOR 4G (EIF4G) DURING ANTI-FAS IGM-INDUCED APOPTOSIS DOES NOT REQUIRE SIGNALING THROUGH THE P38 MITOGEN-ACTIVATED PROTEIN (MAP) KINASE

Initiation factor (eIF) 4G plays a key role in the regulation of trans lation, acting as a bridge between eIF4E and eIF3, to allow an mRNA mo lecule 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 synt hesis and cell death. These responses were prevented by the caspase in hibitors, zVAD.FMK and zDEVD.FMK. We also show that, in contrast to Sa ccharomyces cerevisiae, although rapamycin caused a modest inhibition of protein synthesis it did not induce apoptosis or the cleavage of eI F4G, Studies with the specific inhibitor, SB203580, have shown that si gnalling through the p38 MAP kinase pathway is not required for either the Fas/CD95-induced cleavage of eIF4G or cell death, These data sugg est that the cleavage of eIF4G and the inhibition of translation play an integral role in Fas/CD95-induced cell death in Jurkat cells. (C) 1 998 Federation of European Biochemical Societies.