Participation of the human p53 3'UTR in translational repression and activation following gamma-irradiation.

Abstract

p53 protein levels have been shown to increase in a number of cells after treatment with genotoxic agents through a post-transcriptional mechanism. In gamma-irradiated human cells, the accumulation of p53 protein is accompanied by an increase in the association of p53 mRNA with large polysomes without any change in the level of p53 mRNA. This redistribution of p53 mRNA on polysomes in response to irradiation is consistent with enhanced translational activity of p53 mRNA. We demonstrate that a region of the p53 3'-untranslated region (3'UTR) inhibits translation of a chimeric reporter mRNA in vivo. Induced elevation of reporter activity after gamma-irradiation was seen in cells expressing chimeric reporter-p53 3'UTR transcripts. These data taken together demonstrate translational control of p53 gene expression after gamma-irradiation and denote a previously unsuspected and novel role for the p53 3'UTR in controlling translation.