Nrf2 and Nrf1 in association with Jun proteins regulate antioxidant response element-mediated expression and coordinated induction of genes encoding detoxifying enzymes

Oncogene. 1998 Dec 17;17(24):3145-56. doi: 10.1038/sj.onc.1202237.

Abstract

Antioxidant response element (ARE)-mediated expression and coordinated induction of genes encoding detoxifying enzymes is one mechanism of critical importance to cellular protection against oxidative stress. In the present report, we demonstrate that nuclear transcription factors Nrf2 and Nrf1 associate with Jun (c-Jun, Jun-B and Jun-D) proteins to upregulate ARE-mediated expression and coordinated induction of detoxifying enzymes in response to antioxidants and xenobiotics. Nrf-Jun association/heterodimerization and binding to the ARE required unknown cytosolic factor(s). Nrf2 containing one mutated leucine in its leucine zipper region was more efficient in upregulation of ARE-mediated gene expression, as compared to Nrf1 with two mutated leucines.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antioxidants / pharmacology
  • Binding Sites
  • Collagenases / genetics*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation*
  • Glutathione Transferase / genetics*
  • Humans
  • Leucine Zippers* / genetics
  • Molecular Sequence Data
  • NAD(P)H Dehydrogenase (Quinone) / genetics*
  • NF-E2-Related Factor 1
  • NF-E2-Related Factor 2
  • Nuclear Respiratory Factor 1
  • Nuclear Respiratory Factors
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / metabolism*
  • Rats
  • Sequence Homology, Amino Acid
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Tumor Cells, Cultured
  • beta-Naphthoflavone / pharmacology

Substances

  • Antioxidants
  • DNA-Binding Proteins
  • NF-E2-Related Factor 1
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • NRF1 protein, human
  • Nfe2l1 protein, rat
  • Nfe2l2 protein, rat
  • Nuclear Respiratory Factor 1
  • Nuclear Respiratory Factors
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • Trans-Activators
  • beta-Naphthoflavone
  • NAD(P)H Dehydrogenase (Quinone)
  • Glutathione Transferase
  • Collagenases