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Regulatory mechanisms controlling gene expression mediated by the antioxidant response element
Truyen Nguyen1, Philip J Sherratt, Cecil B Pickett
1Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA. truyen.nguyen@spcorp.com
Annual Review of Pharmacology and Toxicology
|October 3, 2002
Summary
The transcription factor Nrf2 activates antioxidant and detoxification genes via the antioxidant response element (ARE). Its regulation involves chemical inducers, ARE sequence context, and cell type, influencing gene activity.
Area of Science:
- Molecular Biology
- Biochemistry
- Cellular Biology
Background:
- Gene expression for antioxidative and Phase II detoxification enzymes is induced by electrophilic compounds and phenolic antioxidants.
- This induction is transcriptionally regulated by the antioxidant response element (ARE) in gene promoters.
- The transcription factor Nrf2 is central to ARE-mediated activation, responding to oxidative stress.
Purpose of the Study:
- To review the molecular mechanisms regulating transcriptional activation mediated by the Nrf2-ARE interaction.
- To highlight the factors influencing Nrf2-ARE pathway activity.
Main Methods:
- Literature review of recent studies on Nrf2 and ARE.
- Analysis of molecular mechanisms governing transcriptional regulation.
- Examination of factors affecting enhancer activity.
Main Results:
- Nrf2 is the key transcription factor interacting with the ARE to control gene expression.
- Transcriptional activation is modulated by the ARE's sequence context.
- The chemical nature of inducers and the specific cell type significantly impact ARE activity.
Conclusions:
- The Nrf2-ARE pathway is a critical regulator of cellular defense mechanisms.
- Understanding the interplay between ARE sequence, inducers, and cell type is crucial for predicting and manipulating gene expression in response to oxidative stress.