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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

p53 suppresses the Nrf2-dependent transcription of antioxidant response genes

Raffaella Faraonio1, Paola Vergara, Domenico Di Marzo

  • 1Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, CEINGE Biotecnologie avanzate, 80131 Napoli, Italy.

The Journal of Biological Chemistry
|November 2, 2006
PubMed

Insights

The p53 protein suppresses the Nrf2 pathway, which normally activates antioxidant genes. This interaction is crucial for allowing oxidative stress-induced apoptosis by preventing an overly antioxidant cellular environment.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • Cells activate antioxidant genes via the Nrf2 pathway in response to oxidative stress.
  • Oxidative stress-induced DNA damage triggers the p53 pathway, leading to cell cycle arrest or apoptosis.

Purpose of the Study:

  • To investigate the cross-talk between the Nrf2 and p53 regulatory pathways.
  • To determine how p53 influences Nrf2-mediated antioxidant gene transcription.

Main Methods:

  • Overexpression of Nrf2 and p53.
  • Exposure to electrophiles (diethylmaleate).
  • Chromatin immunoprecipitation assays.

Main Results:

  • p53 counteracts Nrf2-induced transcription of antioxidant genes (x-CT, NQO1, GST-alpha1).
  • p53 overexpression or activation blocks the accumulation of antioxidant gene transcripts.
  • p53 directly interacts with antioxidant response elements (AREs) in gene promoters.

Conclusions:

  • p53 negatively regulates Nrf2 transactivation of antioxidant genes.
  • This repression is mediated by p53 binding to AREs.
  • The p53-mediated suppression prevents excessive antioxidant conditions, facilitating p53-induced apoptosis.

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