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Novel insights into the regulation of antioxidant-response-elementmediated gene expression by electrophiles: induction of the transcriptional repressor BACH1 by Nrf2
- Source :
- Biochemical Journal, Biochemical Journal, Portland Press, 2011, 440 (2), pp.167-174. ⟨10.1042/BJ20110526⟩
- Publication Year :
- 2011
- Publisher :
- Portland Press Ltd., 2011.
-
Abstract
- A central mechanism in cellular defence against oxidative or electrophilic stress is mediated by transcriptional induction of genes via the ARE (antioxidant-response element), a cis-acting sequence present in the regulatory regions of genes involved in the detoxification and elimination of reactive oxidants and electrophiles. The ARE binds different bZIP (basic-region leucine zipper) transcription factors, most notably Nrf2 (nuclear factor-erythroid 2-related factor 2) that functions as a transcriptional activator via heterodimerization with small Maf proteins. Although ARE activation by Nrf2 is relatively well understood, the mechanisms by which ARE-mediated signalling is down-regulated are poorly known. Transcription factor BACH1 [BTB (broad-complex, tramtrack and bric-a-brac) and CNC (cap'n'collar protein) homology 1] binds to ARE-like sequences, functioning as a transcriptional repressor in a subset of ARE-regulated genes, thus antagonizing the activator function of Nrf2. In the present study, we have demonstrated that BACH1 itself is regulated by Nrf2 as it is induced by Nrf2 overexpression and by Nrf2-activating agents in an Nrf2-dependent manner. Furthermore, a functional ARE site was identified at +1411 from the transcription start site of transcript variant 2 of BACH1. We conclude that BACH1 is a bona fide Nrf2 target gene and that induction of BACH1 by Nrf2 may serve as a feedback-inhibitory mechanism for ARE-mediated gene regulation.
- Subjects :
- Leucine zipper
NF-E2-Related Factor 2
Oleic Acids
Biology
Response Elements
digestive system
environment and public health
Biochemistry
03 medical and health sciences
0302 clinical medicine
Isothiocyanates
Maf Transcription Factors
Gene expression
Human Umbilical Vein Endothelial Cells
Humans
Molecular Biology
Transcription factor
030304 developmental biology
Regulation of gene expression
Genetics
0303 health sciences
ATF3
Activator (genetics)
Life Sciences
Cell Biology
respiratory system
Nitro Compounds
Fanconi Anemia Complementation Group Proteins
Cell biology
Basic-Leucine Zipper Transcription Factors
HEK293 Cells
Regulatory sequence
Sulfoxides
030220 oncology & carcinogenesis
Thiocyanates
Subjects
Details
- ISSN :
- 14708728 and 02646021
- Volume :
- 440
- Database :
- OpenAIRE
- Journal :
- Biochemical Journal
- Accession number :
- edsair.doi.dedup.....e4e5c3ae452e4718e105c59f1d2baeba