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

Clemens, M. J., Bushell, M. and Morley, S. J. (1998) Degradation of eukaryotic polypeptide chain initiation factor (eIF) 4G in response to induction of apoptosis in human lymphoma cell lines. Oncogene, 17(22), pp. 2921-2931. (doi: 10.1038/sj.onc.1202227) (PMID:9879998)

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We have investigated the effect of inducing apoptosis in BJAB and Jurkat cells on the cellular content of several polypeptide chain initiation factors. Serum deprivation results in inhibition of protein synthesis and induction of apoptosis in BJAB cells; at early times, there is selective degradation of polypeptide initiation factor eIF4G but no major losses of other key initiation 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 similar effects. Both total cytoplasmic eIF4G and eIF4G associated with eIF4E are 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 degradation and blocks the appearance of the ca. 76 kDa product. Exposure of BJAB cells to rapamycin rapidly inhibits protein synthesis but does not lead to acute degradation of eIF4G. In both BJAB and Jurkat cells induction of apoptosis 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 substrate for proteases activated during this process.

Item Type:Articles
Additional Information:The research was supported by grants from The Royal Society, the Wellcome Trust, the Cancer Prevention Research Trust and the Leukaemia Research Fund. MB is funded by an Industrial CASE Studentship in collaboration with Roche Discovery (Welwyn Garden City) and SJM is a Senior Research Fellow of the Wellcome Trust.
Glasgow Author(s) Enlighten ID:Bushell, Professor Martin
Authors: Clemens, M. J., Bushell, M., and Morley, S. J.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Oncogene
Publisher:Springer Nature
ISSN (Online):1476-5594

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