Regulatory mechanisms controlling gene expression mediated by the antioxidant response element

Annu Rev Pharmacol Toxicol. 2003:43:233-60. doi: 10.1146/annurev.pharmtox.43.100901.140229. Epub 2002 Jan 10.


The expression of genes encoding antioxidative and Phase II detoxification enzymes is induced in cells exposed to electrophilic compounds and phenolic antioxidants. Induction of these enzymes is regulated at the transcriptional level and is mediated by a specific enhancer, the antioxidant response element or ARE, found in the promoter of the enzyme's gene. The transcription factor Nrf2 has been implicated as the central protein that interacts with the ARE to activate gene transcription constitutively or in response to an oxidative stress signal. This review focuses on the molecular mechanisms whereby the transcriptional activation mediated by the interaction between the ARE and NF-E2-related factor 2 (Nrf2) is regulated. Recent studies suggest that the sequence context of the ARE, the nature of the chemical inducers, and the cell type are important for determining the activity of the enhancer in a particular gene.

Publication types

  • Review

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • DNA-Binding Proteins / genetics
  • Humans
  • NF-E2-Related Factor 2
  • Rats
  • Response Elements / genetics*
  • Signal Transduction / genetics*
  • Trans-Activators / genetics
  • Transcriptional Activation*


  • Antioxidants
  • DNA-Binding Proteins
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Nfe2l2 protein, rat
  • Trans-Activators