Gene regulatory effects of disease-associated variation in the NRF2 network.

Citation data:

Current opinion in toxicology, ISSN: 2468-2934, Vol: 1, Page: 71-79

Publication Year:
2016
Usage 2
Abstract Views 2
Captures 15
Readers 15
Citations 5
Citation Indexes 5
PMID:
28203648
DOI:
10.1016/j.cotox.2016.09.001
Author(s):
Lacher, Sarah E; Slattery, Matthew
Publisher(s):
Elsevier BV
Tags:
Pharmacology, Toxicology and Pharmaceutics
article description
Reactive oxygen species (ROS), which are both a natural byproduct of oxidative metabolism and an undesirable byproduct of many environmental stressors, can damage all classes of cellular macromolecules and promote diseases from cancer to neurodegeneration. The actions of ROS are mitigated by the transcription factor NRF2, which regulates expression of antioxidant genes via its interaction with -regulatory antioxidant response elements (AREs). However, despite the seemingly straightforward relationship between the opposing forces of ROS and NRF2, regulatory precision in the NRF2 network is essential. Genetic variants that alter NRF2 stability or alter ARE sequences have been linked to a range of diseases. NRF2 hyperactivating mutations are associated with tumorigenesis. On the subtler end of the spectrum, single nucleotide variants (SNVs) that alter individual ARE sequences have been linked to neurodegenerative disorders including progressive supranuclear palsy and Parkinson's disease, as well as other diseases. Although the human health implications of NRF2 dysregulation have been recognized for some time, a systems level view of this regulatory network is beginning to highlight key NRF2-targeted AREs consistently associated with disease.