Two internal ribosome entry sites mediate the translation of p53 isoforms

The p53 tumour suppressor protein has a crucial role in cell‐cycle arrest and apoptosis. Previous reports show that the p53 messenger RNA is translated to produce an amino‐terminal‐deleted isoform (ΔN‐p53) from an internal initiation codon, which acts as a dominant‐negative inhibitor of full‐length p53. Here, we show that two internal ribosome entry sites (IRESs) mediate the translation of both full‐length and ΔN‐p53 isoforms. The IRES directing the translation of full‐length p53 is in the 5′‐untranslated region of the mRNA, whereas the IRES mediating the translation of ΔN‐p53 extends into the protein‐coding region. The two IRESs show distinct cell‐cycle phase‐dependent activity, with the IRES for full‐length p53 being active at the G2–M transition and the IRES for ΔN‐p53 showing highest activity at the G1–S transition. These results indicate a novel translational control of p53 gene expression and activity.

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