ArticleThe Journal of biological chemistry2008
Multiple nuclear localization signals function in the nuclear import of the transcription factor Nrf2.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 128 papers, 1 of them a synthesis that pooled it.
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Who cites it
128 citing papers in PubMed, 1 synthesis or guideline pooled it, 199 citations in OpenAlex.
- Dual roles and therapeutic potential of Keap1-Nrf2 pathway in pancreatic cancer: a systematic review.Cell communication and signaling : CCS · 2019Pooled it
- Cysteine-based molecular switches: a focus on KEAP1 and BACH1 in regulating the antioxidant response.Archives of toxicology · 2026Review
- Effects of Fractionated Low Dose Ionizing Radiation on Cellular Senescence in Mouse Lung Tissue.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- The role of NRF2 in human cancers: Pre-clinical insights paving the way for clinical trials.Journal of pharmaceutical analysis · 2026Review
- BRD4 modulates antimicrobial defense via non-canonical NRF2 activation in macrophages to confer protection against sepsis.PLoS pathogens · 2026Article
- Article
- Varespladib attenuatesRedox report : communications in free radical research · 2025Article
- Beyond Antioxidants: The Emerging Role of Nrf2 Activation in Amyotrophic Lateral Sclerosis (ALS).International journal of molecular sciences · 2025Review
- SIRT5 Alleviated Eosinophilic Asthma Through ROS Inhibition and Nrf2/HO-1 Activation.Inflammation · 2025Article
- Article
- Targeting Nrf2 in acute myeloid leukemia: an updated review on its role in chemoresistance and emerging therapeutic strategies.Medical oncology (Northwood, London, England) · 2025Review
- Oxidative stress response and NRF2 signaling pathway in autism spectrum disorder.Redox biology · 2025Review
- Classification and regulatory interactions of key transcription factors in COVID-19.Frontiers in cellular and infection microbiology · 2025Review
- Alcohol consumption, high-sensitivity C-reactive protein, and estimated glomerular filtration rate: tripartite predictors of 10-year cardiovascular risk progression in patients with type 2 diabetes mellitus after COVID-19.Frontiers in endocrinology · 2025Article
- Mechanistic Insights and Potential Therapeutic Implications of NRF2 in Diabetic Encephalopathy.Molecular neurobiology · 2024Review
- Non-thermal atmospheric pressure plasma induces selective cancer cell apoptosis by modulating redox homeostasis.Cell communication and signaling : CCS · 2024Article
- Multiple types of nuclear localization signals inBiochemistry and biophysics reports · 2024Article
- Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID.NPJ science of food · 2024Review
- The Potential Role of Major Argan Oil Compounds as Nrf2 Regulators and Their Antioxidant Effects.Antioxidants (Basel, Switzerland) · 2024Review
- Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases.Archives of toxicology · 2024Review
68 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Nuclear factor erythroid 2-related factor 2 (Nrf2) mediates the transcriptional response of cells to oxidative stress and is translocated into the nucleus following, or concomitant with, its activation by electrophiles or reactive oxygen species. The mechanism of its translocation into the nucleus is not entirely elucidated. Here we have identified two novel nuclear localization signal (NLS) motifs in murine Nrf2, one located near the N-terminal region (amino acid residues 42-53) and the other (residues 587-593) located near the C-terminal region. Imaging of green fluorescent protein (GFP)-tagged Nrf2 revealed that mutation(s) in any of these sequences resulted in decreased nuclear fluorescence intensity compared with the wild-type Nrf2 when Nrf2 activation was induced with the electrophile tert-butylhydroquinone. The mutations also impaired Nrf2-induced transactivation of antioxidant response element-driven reporter gene expression to the same extent as the Nrf2 construct bearing mutation in a previously identified bipartite NLS that maps at residues 494-511. When linked to GFP or to GFP-PEPCK-C each of the novel NLS motifs was sufficient to drive nuclear translocation of the fusion proteins. Co-immunoprecipitation assays demonstrated that importins alpha5 and beta1 associate with Nrf2, an interaction that was blocked by the nuclear import inhibitor SN50. SN50 also blocked tert-butylhydroquinone-induced nuclear fluorescence of GFP-Nrf2 in cells transfected with wild-type GFP-Nrf2. Overall these results reveal that multiple NLS motifs in Nrf2 function in its nuclear translocation in response to pro-oxidant stimuli and that the importin alpha-beta heterodimer nuclear import receptor system plays a critical role in the import process.
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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.