Nrf2 is associated with the regulation of basal transcription activity of the BRCA1 gene

Acta Biochim Biophys Sin (Shanghai). 2013 Mar;45(3):179-87. doi: 10.1093/abbs/gmt001. Epub 2013 Jan 24.

Abstract

BRCA1 is closely related to the pathogenesis of breast cancer. The activity of BRCA1 promoter is regulated by transcriptional factors. The transcription factor Nrf2 (Nuclear factor-erythroid-2p45-related factor 2) is a potent transcriptional activator and plays a central role in inducible expression of many cytoprotective genes. In this report, we found that over-expression of Nrf2 stimulated BRCA1 expression, knockdown of Nrf2 attenuated BRCA1 expression. Nrf2 also interacted with CBP and p300 to form an active transcription complex, which could bind to the ARE (antioxidant response element) site on the BRCA1 promoter and activate its transcription by inducing histone acetylation. Our finding could lead to a better understanding of the development of breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / metabolism
  • BRCA1 Protein / metabolism*
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • E1A-Associated p300 Protein / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, BRCA1
  • Genetic Predisposition to Disease
  • Histones / metabolism
  • Humans
  • Mutagenesis
  • NF-E2-Related Factor 2 / metabolism*
  • Peptide Fragments / metabolism
  • Promoter Regions, Genetic
  • Response Elements
  • Sialoglycoproteins / metabolism
  • Transcriptional Activation

Substances

  • Antioxidants
  • BRCA1 Protein
  • Histones
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Peptide Fragments
  • Sialoglycoproteins
  • bone sialoprotein (35-62), human
  • E1A-Associated p300 Protein
  • EP300 protein, human