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Yeast As a Chassis for Developing Functional Assays to Study Human P53
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Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

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p53 binds the mdmx mRNA and controls its translation

A-S Tournillon1, I López1, L Malbert-Colas1

  • 1Equipe Labellisée la Ligue Contre le Cancer, Institut National de la Santé et de la Recherche Médicale UMR1162, Institut de Génétique Moléculaire, Université Paris 7, Hôpital St Louis, Paris, France.

Oncogene
|July 5, 2016
PubMed

Insights

The tumor suppressor p53 directly inhibits the translation of MDMX mRNA, adding a new layer to the p53 regulatory feedback loop. This discovery highlights the crucial role of mRNA translation control in the p53 pathway.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Gene Regulation

Background:

  • MDMX and MDM2 are key regulators of the p53 tumor suppressor.
  • While MDM2-p53 interactions are well-studied, p53-MDMX regulatory pathways remain less understood.
  • p53 controls gene expression via transcriptional and post-transcriptional mechanisms.

Purpose of the Study:

  • To investigate the regulatory relationship between p53 and MDMX.
  • To elucidate the mechanisms by which p53 influences MDMX protein levels.
  • To explore the role of mRNA translation control in the p53 pathway.

Main Methods:

  • In vitro and cell-based assays to study mRNA translation.
  • RNA-binding assays using p53 core domain and 5' UTR of mdmx mRNA.
  • Zinc-dependent binding studies.
  • Reporter assays with fused mdmx 5'UTR and ovalbumin.
  • Analysis of p53 mutant R273H RNA-binding profile.

Main Results:

  • Overexpression of p53 suppresses mdmx mRNA translation.
  • The p53 core domain binds the 5' UTR of mdmx mRNA in a zinc-dependent manner.
  • p53's N-terminus trans-suppression domain further controls MDMX synthesis.
  • Fusion of mdmx 5'UTR to ovalbumin suppresses ovalbumin synthesis.
  • The p53 mutant R273H exhibits altered RNA-binding and differentiates MDMX isoform synthesis.

Conclusions:

  • p53 acts as a trans-suppressor of mdmx mRNA, inhibiting its translation.
  • This finding reveals a novel feedback mechanism in the p53 regulatory network.
  • mRNA translation control is a critical component of p53 pathway regulation.

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