ArticleThe Journal of biological chemistry2011
Acetylation-deacetylation of the transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) regulates its transcriptional activity and nucleocytoplasmic localization.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 181 papers.
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Who cites it
181 citing papers in PubMed, 346 citations in OpenAlex.
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- HDAC1 Represses NRF2 Transcription via H3K27ac Remodeling to Aggravate Neomycin-Induced Cochlear Hair Cell Damage.Neurochemical research · 2026Article
- Pyrroloquinoline Quinone and NADPharmaceuticals (Basel, Switzerland) · 2026Review
- Interplay between NRF2 post-translational modifications and protein-protein interactions: Perspectives from emerging structural and functional evidence.Archives of biochemistry and biophysics · 2026Review
- Article
- Beyond KEAP1: The Context-Specific NRF2 Partner Code in Disease and Therapy.Antioxidants (Basel, Switzerland) · 2026Review
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- ACLY Safeguards Copper Homeostasis to Sustain Brown Adipose Tissue Thermogenesis and Restrain Diet-Induced Obesity.Research (Washington, D.C.) · 2026Article
- Cold Atmospheric Plasma Enhances Fn14 Signaling in Hair Follicle Stem Cells, Thereby Promoting the Healing of Diabetic Skin Wounds in a Mouse Model.Journal of immunology research · 2026Article
- Micro- and Nanoplastics and Functional Nutrients in Human Health: Epigenetic Mechanisms and Cellular Resilience Signaling in Brain Insulin Resistance and the Risk of Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Modulation of Nrf2 and Mitochondrial Function: Pharmacological Implications.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Modulating nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 in liver-brain axis disorders.World journal of psychiatry · 2025Review
- Regulatory Dynamics of Nrf2 With Sirtuins in the Brain: Exploring Cellular Metabolism, Synaptic Plasticity, and Defense Mechanisms.Journal of neurochemistry · 2025Review
- Natural compounds attenuate combined chromium and arsenic-induced oxidative stress and nephritic apoptosis by activating the Nrf2/Keap1 signaling and associated xenobiotic metabolizing enzymes.Scientific reports · 2025Article
- Liver Metabolism at the Crossroads: The Reciprocal Control of Nutrient-Sensing Nuclear Receptors and Autophagy.International journal of molecular sciences · 2025Review
- Multifaceted roles of melatonin in oncology: an insight into its therapeutic potential in cancer management.Inflammopharmacology · 2025Review
- Targeting epigenetic and post-translational modifications of NRF2: key regulatory factors in disease treatment.Cell death discovery · 2025Review
- Triple regulation of oxidative-acetylation cycling pathways in COPD glucocorticoid resistance by HuaTanJiangQi capsules.3 Biotech · 2025Article
- SIRT7-mediated NRF2 deacetylation promotes antioxidant response and protects against chemodrug-induced liver injury.Cell death & disease · 2025Article
- Article
121 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Activation of Nrf2 by covalent modifications that release it from its inhibitor protein Keap1 has been extensively documented. In contrast, covalent modifications that may regulate its action after its release from Keap1 have received little attention. Here we show that CREB-binding protein induced acetylation of Nrf2, increased binding of Nrf2 to its cognate response element in a target gene promoter, and increased Nrf2-dependent transcription from target gene promoters. Heterologous sirtuin 1 (SIRT1) decreased acetylation of Nrf2 as well as Nrf2-dependent gene transcription, and its effects were overridden by dominant negative SIRT1 (SIRT1-H355A). The SIRT1-selective inhibitors EX-527 and nicotinamide stimulated Nrf2-dependent gene transcription, whereas resveratrol, a putative activator of SIRT1, was inhibitory, mimicking the effect of SIRT1. Mutating lysine to alanine or to arginine at Lys(588) and Lys(591) of Nrf2 resulted in decreased Nrf2-dependent gene transcription and abrogated the transcription-activating effect of CREB-binding protein. Furthermore, SIRT1 had no effect on transcription induced by these mutants, indicating that these sites are acetylation sites. Microscope imaging of GFP-Nrf2 in HepG2 cells as well as immunoblotting for Nrf2 showed that acetylation conditions resulted in increased nuclear localization of Nrf2, whereas deacetylation conditions enhanced its cytoplasmic rather than its nuclear localization. We posit that Nrf2 in the nucleus undergoes acetylation, resulting in binding, with basic-region leucine zipper protein(s), to the antioxidant response element and consequently in gene transcription, whereas deacetylation disengages it from the antioxidant response element, thereby resulting in transcriptional termination and subsequently in its nuclear export.
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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.