Degradation of eukaryotic polypeptide chain initiation factor (eIF) 4G in response to induction of apoptosis in human lymphoma cell lines

We have investigated the effect of inducing apoptosis in BJAB and Jurkat ce lls on the cellular content of several polypeptide chain initiation factors . Serum deprivation results in inhibition of protein synthesis and inductio n of apoptosis in BJAB cells; at early times, there is selective degradatio n of polypeptide initiation factor eIF4G but no major losses of other key i nitiation factors. The disappearance of full length eIF4G is accompanied by the appearance of smaller forms of the protein, including a major product of approximately 76 kDa. Apoptosis induced by cycloheximide results in simi lar effects. Both total cytoplasmic eIF4G and eIF4G associated with eIF4E a re degraded with a half-life of 2-4 h under these conditions. Treatment of serum-starved or cycloheximide-treated cells with Z-VAD.FMK or Z-DEVD.FMK, which inhibit caspases required for apoptosis, protects eIF4G from degradat ion and blocks the appearance of the ca. 76 kDa product. Exposure of BJAB c ells to rapamycin rapidly inhibits protein synthesis but does not lead to a cute degradation of eIF4G. In both BJAB and Jurkat cells induction of apopt osis with anti-Fas antibody or etoposide also results in the selective loss of eIF4G, which is inhibitable by Z-VAD.FMK. These data suggest that eIF4G is selectively targeted for cleavage as cells undergo apoptosis and is a s ubstrate for proteases activated during this process.