Related Experiment Video

Updated: Nov 15, 2025

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
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Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

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p53-R273H Sustains ROS, Pro-Inflammatory Cytokine Release and mTOR Activation While Reducing Autophagy, Mitophagy and

Maria Anele Romeo1,2, Maria Saveria Gilardini Montani1,2, Rossella Benedetti1,2

  • 1Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy.

Biomolecules
|March 6, 2021
PubMed

Insights

Mutant p53 (mutp53) promotes cancer by increasing reactive oxygen species (ROS) and inflammation. Wild-type p53 (wtp53) can counteract these tumor-promoting effects, potentially explaining less aggressive cancers with heterozygous mutp53.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • The p53 gene is frequently inactivated in cancer, and its mutant forms can promote tumor progression.
  • Mutant p53 (mutp53) proteins can acquire oncogenic functions, interacting with pro-tumorigenic pathways.
  • Oncogenic pathway activation is linked to reactive oxygen species (ROS) and inflammation, creating a pro-tumorigenic environment.

Purpose of the Study:

  • To investigate the role of the specific mutant p53-R273H in promoting cancer cell survival and the tumor microenvironment.
  • To explore the interplay between mutant p53, ROS, inflammation, and key cellular pathways like mTOR and autophagy.
  • To determine if wild-type p53 (wtp53) can counteract the pro-tumorigenic effects of p53-R273H.

Main Methods:

  • Experiments involved silencing and transfecting the p53-R273H mutant.
  • Assessed intracellular ROS levels, pro-inflammatory cytokine release, mTOR activation, autophagy/mitophagy, and uncoupling protein 2 (UCP2) expression.
  • Transfected p53-R273H into cancer cells expressing wild-type p53 (wtp53) for comparative analysis.

Main Results:

  • p53-R273H silencing reduced cancer cell survival, while its transfection increased intracellular ROS and pro-inflammatory/immune-suppressive cytokine release.
  • Mutant p53 (mutp53) activated mTOR, reduced autophagy and mitophagy, and downregulated UCP2.
  • Transfecting p53-R273H into wtp53-expressing cells did not induce these pro-tumorigenic effects and led to p21 upregulation.

Conclusions:

  • Mutant p53 (mutp53) actively promotes cancer cell survival and a pro-tumorigenic milieu through ROS and inflammation.
  • Wild-type p53 (wtp53) appears to possess counteracting functions against the oncogenic activities of specific mutp53 forms.
  • The presence of wtp53 may mitigate the aggressiveness of cancers with heterozygous mutp53 compared to homozygous mutp53.
Keywords:
ROScancercytokinesmutp53wtp53

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