p53 activation results in rapid dephosphorylation of the eIF4E-binding protein 4E-BP1, inhibition of ribosomal protein S6 kinase and inhibition of translation initiation

Horton, L. E., Bushell, M. , Barth-Baus, D., Tilleray, V. J., Clemens, M. J. and Hensold, J. O. (2002) p53 activation results in rapid dephosphorylation of the eIF4E-binding protein 4E-BP1, inhibition of ribosomal protein S6 kinase and inhibition of translation initiation. Oncogene, 21(34), pp. 5325-5334. (doi: 10.1038/sj.onc.1205662) (PMID:12149653)

Abstract

p53 is an important regulator of cell cycle progression and apoptosis, and inactivation of p53 is associated with tumorigenesis. Although p53 exerts many of its effects through regulation of transcription, this protein is also found in association with ribosomes and several mRNAs have been identified that are translationally controlled in a p53-dependent manner. We have utilized murine erythroleukemic cells that express a temperature-sensitive p53 protein to determine whether p53 also functions at the level of translation. The data presented here demonstrate that p53 causes a rapid decrease in translation initiation. Analysis of several potential mechanisms for regulating protein synthesis shows that p53 has selective effects on the phosphorylation of the eIF4E-binding protein, 4E-BP1, and the activity of the p70 ribosomal protein S6 kinase. These data provide evidence that modulation of translational activity constitutes a further mechanism by which the growth inhibitory effects of p53 may be mediated.

• Item Type: Articles
• Additional Information: Research in our laboratories is supported by the Office of Research and Development, Medical Research Service, Department of Veterans’ Affairs (JO Hensold) and grants from the NIH (DK43414) (JO Hensold), (HK07147-21A1) (LE Horton), the Wellcome Trust (056778), the Leukemia Research Fund, the Cancer Prevention Research Trust and Glaxo-Wellcome (MJ Clemens).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Bushell, Professor Martin
• Authors: Horton, L. E., Bushell, M., Barth-Baus, D., Tilleray, V. J., Clemens, M. J., and Hensold, J. O.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Oncogene
• Publisher: Springer Nature
• ISSN: 0950-9232
• ISSN (Online): 1476-5594