title: Nrf2 and Nrf1 in association with Jun proteins regulate antioxidant response element-mediated expression and coordinated induction of genes encoding detoxifying enzymes.
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.
authors.affiliation: Department of Pharmacology, Baylor College of Medicine, Texas 77030-3498, USA.
authors.forename: R
authors.initials: R
authors.lastname: Venugopal
authors.forename: A K
authors.initials: AK
authors.lastname: Jaiswal
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001665:Binding Sites; D017364:Collagenases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D016350:Leucine Zippers / Q000235:genetics; D008969:Molecular Sequence Data; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D051265:NF-E2-Related Factor 1; D051267:NF-E2-Related Factor 2; D051266:Nuclear Respiratory Factor 1; D051264:Nuclear Respiratory Factors; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D019324:beta-Naphthoflavone / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D004268:DNA-Binding Proteins; D051265:NF-E2-Related Factor 1; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C495633:NRF1 protein, human; C495632:Nfe2l1 protein, rat; C495637:Nfe2l2 protein, rat; D051266:Nuclear Respiratory Factor 1; D051264:Nuclear Respiratory Factors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D015534:Trans-Activators; D019324:beta-Naphthoflavone; D016660:NAD(P)H Dehydrogenase (Quinone); D005982:Glutathione Transferase; D017364:Collagenases