Tonelli, C., Chio, I. I. C., Tuveson, D. A. (September 2017) Transcriptional regulation by Nrf2. Antioxid Redox Signal. ISSN 1523-0864
Abstract
SIGNIFICANCE: Nrf2 is a transcription factor that coordinates the basal and stress-inducible activation of a vast array of cytoprotective genes. Understanding the regulation of Nrf2 activity and downstream pathways has major implications for human health. Recent Advances: Nrf2 regulates the transcription of components of the glutathione and thioredoxin antioxidant systems, as well as enzymes involved in phase I and phase II detoxification of exogenous and endogenous products, NADPH regeneration, and heme metabolism. It therefore represents a crucial regulator of the cellular defense mechanisms against xenobiotic and oxidative stress. In addition to antioxidant responses, Nrf2 is involved in other cellular processes, such as autophagy, intermediary metabolism, stem cell quiescence and unfolded protein response. Given the wide range of processes that Nrf2 controls, its activity is tightly regulated at multiple levels. Here, we review the different modes of regulation of Nrf2 activity and the current knowledge of Nrf2-mediated transcriptional control. CRITICAL ISSUES: It is now clear that Nrf2 lies at the center of a complex regulatory network. A full comprehension of the Nrf2 program will require an integrated consideration of all the different factors determining Nrf2 activity. FUTURE DIRECTIONS: Additional computational and experimental studies are needed to obtain a more dynamic global view of Nrf2-mediated gene regulation. In particular, studies comparing how the Nrf2-dependent network changes from a physiological to a pathological condition can provide insight into mechanisms of disease and instruct new treatment strategies.
| Item Type: | Paper |
|---|---|
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation |
| CSHL Authors: | |
| Communities: | CSHL labs > Tuveson lab CSHL Cancer Center Program > Cellular Communication in Cancer Program |
| Depositing User: | Matt Covey |
| Date: | 13 September 2017 |
| Date Deposited: | 21 Sep 2017 19:49 |
| Last Modified: | 26 Oct 2020 15:34 |
| PMCID: | PMC6208165 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/35281 |
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