ArticleFree radical biology & medicine2015
Beyond antioxidant genes in the ancient Nrf2 regulatory network.
Article in Free radical biology & medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
45 citing papers in PubMed, 72 citations in OpenAlex.
- Simvastatin as a Potential Disease-Modifying Therapy for Patients with Parkinson's Disease: Rationale for Clinical Trial, and Current Progress.Journal of Parkinson's disease · 2017Trial
- Beyond KEAP1: The Context-Specific NRF2 Partner Code in Disease and Therapy.Antioxidants (Basel, Switzerland) · 2026Review
- Update: Is exercise-induced oxidative stress a friend or foe?Sports medicine and health science · 2026Review
- A Cross-Species Hydroquinone Model Replicates Smoking-Related Corneal Endothelial Oxidative Injury and Enables Therapeutic Screening of FGF10.Investigative ophthalmology & visual science · 2026Article
- Traditional Health Practices May Promote Nrf2 Activation Similar to Exercise.International journal of molecular sciences · 2025Review
- Reactive oxygen species promote endurance exercise-induced adaptations in skeletal muscles.Journal of sport and health science · 2024Review
- Apigenin Ameliorates HPharmaceuticals (Basel, Switzerland) · 2024Article
- Involvement of DPP3 in modulating oncological features and oxidative stress response in esophageal squamous cell carcinoma.Bioscience reports · 2023Article
- Limited expression of Nrf2 in neurons across the central nervous system.Redox biology · 2023Article
- The Triterpenoid Nrf2 Activator, CDDO-Me, Decreases Neutrophil Senescence in a Murine Model of Joint Damage.International journal of molecular sciences · 2023Article
- Limited Expression ofbioRxiv : the preprint server for biology · 2023Article
- Review
- Redox signaling regulates skeletal muscle remodeling in response to exercise and prolonged inactivity.Redox biology · 2022Review
- Article
- NRF2-Dependent Placental Effects Vary by Sex and Dose following Gestational Exposure to Ultrafine Particles.Antioxidants (Basel, Switzerland) · 2022Article
- Neuroligin-1 Is a Mediator of Methylmercury Neuromuscular Toxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Transcriptional reprogramming by oxidative stress occurs within a predefined chromatin accessibility landscape.Free radical biology & medicine · 2021Article
- Deep proteogenomic investigations elucidate the NRF2 antioxidant mechanism as a major driving mechanism of lung adenocarcinoma in Asia.Journal of the Chinese Medical Association : JCMA · 2021Article
- Menopause and the Skin: Old Favorites and New Innovations in Cosmeceuticals for Estrogen-Deficient Skin.Dermatology and therapy · 2021Review
- Pathogenic Mechanisms of Myeloma Bone Disease and Possible Roles for NRF2.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Nrf2, a basic leucine zipper transcription factor encoded by the gene NFE2L2, is a master regulator of the transcriptional response to oxidative stress. Nrf2 is structurally and functionally conserved from insects to humans, and it heterodimerizes with the small MAF transcription factors to bind a consensus DNA sequence (the antioxidant response element, or ARE) and regulate gene expression. We have used genome-wide chromatin immunoprecipitation and gene expression data to identify direct Nrf2 target genes in Drosophila and humans. These data have allowed us to construct the deeply conserved ancient Nrf2 regulatory network-target genes that are conserved from Drosophila to human. The ancient network consists of canonical antioxidant genes, as well as genes related to proteasomal pathways and metabolism and a number of less expected genes. We have also used enhancer reporter assays and electrophoretic mobility-shift assays to confirm Nrf2-mediated regulation of ARE activity at a number of these novel target genes. Interestingly, the ancient network also highlights a prominent negative feedback loop; this, combined with the finding that Nrf2-mediated regulatory output is tightly linked to the quality of the ARE it is targeting, suggests that precise regulation of nuclear Nrf2 concentration is necessary to achieve proper quantitative regulation of distinct gene sets. Together, these findings highlight the importance of balance in the Nrf2-ARE pathway and indicate that Nrf2-mediated regulation of xenobiotic metabolism, glucose metabolism, and proteostasis has been central to this pathway since its inception.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.