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 (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.
Ray
Partho Sarothi
PS
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore.
Grover
Richa
R
Das
Saumitra
S
D020121:5' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D002453:Cell Cycle; D045744:Cell Line, Tumor; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D014176:Protein Biosynthesis; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics; D012270:Ribosomes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
D020121:5' Untranslated Regions; D020033:Protein Isoforms; D022821:RNA Splice Sites; D016159:Tumor Suppressor Protein p53