title: The Nrf2 regulatory network provides an interface between redox and intermediary metabolism.
abstract: Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2, also called Nfe2l2) is a transcription factor that regulates the cellular redox status. Nrf2 is controlled through a complex transcriptional/epigenetic and post-translational network that ensures its activity increases during redox perturbation, inflammation, growth factor stimulation and nutrient/energy fluxes, thereby enabling the factor to orchestrate adaptive responses to diverse forms of stress. Besides mediating stress-stimulated induction of antioxidant and detoxification genes, Nrf2 contributes to adaptation by upregulating the repair and degradation of damaged macromolecules, and by modulating intermediary metabolism. In the latter case, Nrf2 inhibits lipogenesis, supports β-oxidation of fatty acids, facilitates flux through the pentose phosphate pathway, and increases NADPH regeneration and purine biosynthesis; these observations suggest Nrf2 directs metabolic reprogramming during stress.
authors.affiliation: Jacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK. Electronic address: j.d.hayes@dundee.ac.uk.
authors.forename: John D
authors.initials: JD
authors.lastname: Hayes
authors.affiliation: Jacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK.
authors.forename: Albena T
authors.initials: AT
authors.lastname: Dinkova-Kostova
mesh_terms: D005786:Gene Expression Regulation; D006801:Humans; D050356:Lipid Metabolism; D053858:Metabolic Networks and Pathways; D008928:Mitochondria / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction
chemical_list: D051267:NF-E2-Related Factor 2
keywords: GSK-3; Keap1; NADPH; Nrf2; fatty acid β-oxidation; glutathione; oxidative stress; pentose phosphate pathway; purine synthesis.; thioredoxin; β-TrCP