期刊
ONCOGENE
卷 21, 期 34, 页码 5325-5334出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1205662
关键词
growth inhibition; mTOR; p53; polypeptide chain initiation; protein synthesis
资金
- NIDDK NIH HHS [DK43414] Funding Source: Medline
- PHITPO CDC HHS [HK07147-21A1] Funding Source: Medline
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.
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