p53-induced inhibition of protein synthesis is independent of apoptosis

Constantinou, C., Bushell, M. , Jeffrey, I. W., Tilleray, V., West, M., Frost, V., Hensold, J. and Clemens, M. J. (2003) p53-induced inhibition of protein synthesis is independent of apoptosis. European Journal of Biochemistry, 270(15), pp. 3122-3132. (doi:10.1046/j.1432-1033.2003.03687.x) (PMID:12869187)

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Abstract

Activation of a temperature‐sensitive form of p53 in murine erythroleukaemia cells results in a rapid impairment of protein synthesis that precedes inhibition of cell proliferation and loss of cell viability by several hours. The inhibition of translation is associated with specific cleavages of polypeptide chain initiation factors eIF4GI and eIF4B, a phenomenon previously observed in cells induced to undergo apoptosis in response to other stimuli. Although caspase activity is enhanced in the cells in which p53 is activated, both the effects on translation and the cleavages of the initiation factors are completely resistant to inhibition of caspase activity. Moreover, exposure of the cells to a combination of the caspase inhibitor z‐VAD.FMK and the survival factor erythropoietin prevents p53‐induced cell death but does not reverse the inhibition of protein synthesis. We conclude that the p53‐regulated cleavages of eIF4GI and eIF4B, as well as the overall inhibition of protein synthesis, are caspase‐independent events that can be dissociated from the induction of apoptosis per se.

Item Type:Articles
Additional Information:This research was supported by grants to M. J. Clemens from the Wellcome Trust (056778), the Leukaemia Research Fund and Glaxo- Wellcome and by grants to J. Hensold from the Office of Research and Development, Medical Research Service, Department of Veterans’ Affairs and the NIH (DK43414). J. Hensold was also funded during a period of sabbatical leave by an award from Burroughs-Wellcome. C. Constantinou is supported by a PhD studentship from the Cancer Prevention Research Trust, with additional funding from the AG Leventis Foundation and an Overseas Research Scholarship from Universities UK. M. Bushell is supported by a Fellowship from The Wellcome Trust (063233).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bushell, Professor Martin
Authors: Constantinou, C., Bushell, M., Jeffrey, I. W., Tilleray, V., West, M., Frost, V., Hensold, J., and Clemens, M. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:European Journal of Biochemistry
Publisher:Wiley
ISSN:0014-2956
ISSN (Online):1432-1033
Published Online:30 June 2003

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