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IRES mediated translational regulation of p53 isoforms

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p53 is a well known tumor suppressor protein that plays a critical role in cell cycle arrest and apoptosis. It has several isoforms which are produced by transcriptional and posttranscriptional regulatory mechanisms. p53 mRNA has been demonstrated to be translated into two isoforms, full‐length p53 (FL‐p53) and a truncated isoform ΔN‐p53 by the use of alternative translation initiation sites. The mechanism of translation regulation of these two isoforms was further elucidated by the discovery of IRES elements in the p53 mRNA. These two IRESs were shown to regulate the translation of p53 and ΔN‐p53 in a distinct cell‐cycle phase‐dependent manner. This review focuses on the current understanding of the regulation of p53 IRES mediated translation and the role of cis and trans acting factors that influence expression of p53 isoforms. WIREs RNA 2014, 5:131–139. doi: 10.1002/wrna.1202 This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein–RNA Recognition RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications Translation > Translation Regulation

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Schematic representation of p53 mRNA showing two IRES elements. The two AUG codons are depicted in p53mRNA, first AUG positioned after 134nts responsible for full length p53 (FL‐p53), second AUG positioned after 251nts responsible for ΔN‐p53 synthesis.
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Representation of proposed regulation of p53 IRES mediated translation. During stress and physiological conditions IRES trans‐acting factors (green: DAP5, brown: hnRNPC1/C2, purple: PTB, yellow: ANXA2, and red: RPL26) come out from nucleus to cytoplasm to enhance IRES activity.
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(a) p53 translation regulation. ITAFs binding to the IRESs (purple: PTB, yellow: ANXA2, red: hnRNPC1/C2, and green: PSF) enhances translation. miRNAs binding to p53 3′UTR inhibits translation. (b) Circularization of p53 mRNA helps in translation. (1) Circularization of p53 mRNA through PABP and cap of mRNA. (2) 5′–3′UTR interaction with help of RPL26.
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RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications
Translation > Translation Regulation
RNA Interactions with Proteins and Other Molecules > Protein–RNA Recognition

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