Does Nrf2 contribute to p53-mediated control of cell survival and death?

Weimin Chen, Tao Jiang, Huihui Wang, Shasha Tao, Alexandria Lau, Deyu Fang, Donna D. Zhang

Research output: Contribution to journalReview article

54 Scopus citations

Abstract

In response to oxidative stress, the transcription factor Nrf2 is upregulated and controls activation of many genes that work in concert to defend cells from damages and to maintain cellular redox homeostasis. p53 has been regarded as the guardian of the genome through its pro-oxidant and antioxidant functions. Under low levels of reactive oxygen species (ROS), "normal" amounts of p53 upregulates expression of antioxidant genes, protecting macromolecules from ROS-induced damage. However, at high levels or extended exposure of ROS, p53 expression is enhanced, activating pro-oxidant genes and resulting in p53-dependent apoptosis. We observed a two-phase Nrf2 expression controlled by p53. (i) The induction phase: when p53 expression is relatively low, p53 enhances the protein level of Nrf2 and its target genes to promote cell survival in a p21-dependent manner. (ii) The repression phase: when p53 expression is high, the Nrf2-mediated survival response is inhibited by p53. Our observation leads to the hypothesis that the p53-mediated biphasic regulation of Nrf2 may be key for the tumor-suppressor function of p53 by coordinating cell survival and death pathways.

Original languageEnglish (US)
Pages (from-to)1670-1675
Number of pages6
JournalAntioxidants and Redox Signaling
Volume17
Issue number12
DOIs
StatePublished - Dec 15 2012

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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