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Translation control can shape TP53-dependent cell fate

Dario Rizzotto1, Sara Zaccara1, Annalisa Rossi1

  • 1Department of Cellular, Computational and Integrative Biology, CIBIO, University of Trento, Trento, Italy.

Molecular & Cellular Oncology
|September 18, 2020
PubMed

Insights

Nutlin-3 treatment unleashes p53, revealing a translational control mechanism. RNA binding proteins PCBP2 and DHX30 modulate cell death pathways via p53-dependent transcription.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Cancer Research

Background:

  • Nutlin-3 is an MDM2 inhibitor that activates the p53 tumor suppressor.
  • Cellular responses to p53 activation can vary, indicating complex regulatory mechanisms.
  • Understanding these mechanisms is crucial for developing targeted cancer therapies.

Purpose of the Study:

  • To investigate the mechanisms controlling cellular responses to Nutlin-3.
  • To identify key regulatory factors involved in p53-mediated cellular processes.
  • To elucidate how translational control impacts cell death pathways.

Main Methods:

  • Utilized Nutlin-3 to activate p53 in cellular models.
  • Employed RNA-binding protein analysis to identify key players.
  • Investigated p53-dependent transcriptional and translational outputs.
  • Assessed the modulation of cell death pathway activation.

Main Results:

  • Discovered a translational control mechanism involving RNA binding proteins.
  • Identified PCBP2 and DHX30 as critical components of this mechanism.
  • Demonstrated that this control modulates the activation of cell death pathways.
  • Linked translational control to the broader p53-dependent transcriptional output.

Conclusions:

  • Translational control, mediated by PCBP2 and DHX30, is a key regulator of cellular responses to p53 activation.
  • This mechanism fine-tunes the activation of cell death pathways.
  • Findings offer new insights into p53-driven cancer biology and therapeutic strategies.
Keywords:
DHX30PCBP2apoptosisp53polysomal profilingtranscriptiontranslationtranslatome

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