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Two internal ribosome entry sites mediate the translation of p53 isoforms.

ABSTRACT: 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 (DeltaN-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 DeltaN-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 DeltaN-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 DeltaN-p53 showing highest activity at the G1-S transition. These results indicate a novel translational control of p53 gene expression and activity.

SUBMITTER: Ray PS

PROVIDER: S-EPMC1456917 | biostudies-literature | 2006 Apr

REPOSITORIES: biostudies-literature

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Two internal ribosome entry sites mediate the translation of p53 isoforms.

Ray Partho Sarothi PS Grover Richa R Das Saumitra S

EMBO reports 20060120 4

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 (DeltaN-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 DeltaN-p53 isoforms. The IRES directing the translation of full-length p53 is in t ...[more]

PMID: 16440000

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