p53-induced inhibition of protein synthesis is independent of apoptosis

Constantina Constantinou, Martin Bushell, Ian W. Jeffrey, Vivienne Tilleray, Matthew West, Victoria Frost, Jack Hensold, Michael J. Clemens

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22 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3122-3132
Number of pages11
JournalEuropean Journal of Biochemistry
Volume270
Issue number15
DOIs
Publication statusPublished - Aug 2003

Keywords

  • Caspases
  • Erythroleukaemia
  • p53
  • Protein synthesis
  • Temperature-sensitive mutants

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