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Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling
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Published on: October 28, 2014

Tumor suppressor protein Pdcd4 inhibits translation of p53 mRNA

Lena Wedeken1, Priyanka Singh, Karl-Heinz Klempnauer

  • 1Institut für Biochemie, Westfälische-Wilhelms-Universität Münster, D-48149 Münster, Germany.

The Journal of Biological Chemistry
|October 29, 2011
PubMed

Insights

The tumor suppressor Pdcd4 (programmed cell death protein 4) directly suppresses p53 mRNA translation. DNA damage reduces Pdcd4, releasing this suppression and increasing p53 levels.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Gene Regulation

Background:

  • The tumor suppressor Pdcd4 (programmed cell death protein 4) inhibits translation initiation factor eIF4A's helicase activity.
  • Pdcd4 is known to suppress translation of mRNAs with structured 5' untranslated regions (5'-UTRs).
  • Specific natural target mRNAs regulated by Pdcd4 have remained largely unidentified.

Purpose of the Study:

  • To identify natural mRNA targets of Pdcd4.
  • To investigate the mechanism by which Pdcd4 regulates target mRNA translation.
  • To elucidate the role of Pdcd4 in p53 expression control.

Main Methods:

  • RNA immunoprecipitation assays to detect Pdcd4-mRNA association.
  • Western blotting to assess protein levels.
  • Reporter assays to evaluate translational activity.

Main Results:

  • p53 mRNA was identified as a direct translational target of Pdcd4.
  • Pdcd4 binds to p53 mRNA and suppresses its translation.
  • Suppression is dependent on Pdcd4's interaction with eIF4A and p53 mRNA's structured 5'-UTR.
  • DNA-damaging agents decrease Pdcd4 expression, leading to increased p53 translation.

Conclusions:

  • Pdcd4 directly suppresses the translation of p53 mRNA via its structured 5'-UTR.
  • Pdcd4 plays a role in maintaining low p53 levels in unstressed cells.
  • Reduced Pdcd4 levels after DNA damage abrogate translational suppression, contributing to p53 upregulation.

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