ArticleThe EMBO journal2017
Glycosylation of KEAP1 links nutrient sensing to redox stress signaling.
Article in The EMBO journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 102 citations in OpenAlex.
- Interplay between NRF2 post-translational modifications and protein-protein interactions: Perspectives from emerging structural and functional evidence.Archives of biochemistry and biophysics · 2026Review
- A Function-Centric Framework for Mitochondrial Quality Control.Biomolecules · 2026Review
- O-GlcNAcylation in novel regulated cell death: ferroptosis, pyroptosis, and necroptosis.Cell death discovery · 2025Review
- Nrf2-Keap1 Pathway and NLRP3 Inflammasome in Parkinson's Disease: Mechanistic Crosstalk and Therapeutic Implications.Molecular neurobiology · 2025Review
- Article
- The HBP Pathway Inhibitor FR054 Enhances Temozolomide Sensitivity in Glioblastoma Cells by Promoting Ferroptosis and Inhibiting O-GlcNAcylation.CNS neuroscience & therapeutics · 2025Article
- Is dolichol pathway dysfunction a significant factor in Alzheimer's disease?Inflammopharmacology · 2025Review
- O-linked β-N-acetylglucosamine modification in diabetic foot ulcer pathogenesis.Burns & trauma · 2025Review
- Asiatic acid ameliorates doxorubicin-induced cardiotoxicity by promoting FPN-mediated iron export and inhibiting ferroptosis.Acta pharmacologica Sinica · 2025Article
- O-GlcNAcylation promotes malignancy and cisplatin resistance of lung cancer by stabilising NRF2.Clinical and translational medicine · 2024Article
- Role of O-linked N-acetylglucosamine protein modification in oxidative stress-induced autophagy: a novel target for bone remodeling.Cell communication and signaling : CCS · 2024Review
- Roles of O-GlcNAcylation in Mitochondrial Homeostasis and Cardiovascular Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Nrf2 Pathway and Oxidative Stress as a Common Target for Treatment of Diabetes and Its Comorbidities.International journal of molecular sciences · 2024Review
- Review
- Neurorescuing effect of Cinacalcet against hypercalcemia-induced nerve injury in chronic kidney disease via TRAF2/cIAP1/KLF2/SERPINA3 signal axis.Cell biology and toxicology · 2023Article
- Redox Regulation of Nrf2 in Cisplatin-Induced Kidney Injury.Antioxidants (Basel, Switzerland) · 2023Review
- Extracellular arginine availability modulates eIF2α O-GlcNAcylation and heme oxygenase 1 translation for cellular homeostasis.Journal of biomedical science · 2023Article
- The Complex Genetic and Epigenetic Regulation of the Nrf2 Pathways: A Review.Antioxidants (Basel, Switzerland) · 2023Review
- Post-translational modifications of Keap1: the state of the art.Frontiers in cell and developmental biology · 2023Review
- The untapped potential of targeting NRF2 in neurodegenerative disease.Frontiers in aging · 2023Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
O-GlcNAcylation is an essential, nutrient-sensitive post-translational modification, but its biochemical and phenotypic effects remain incompletely understood. To address this question, we investigated the global transcriptional response to perturbations in O-GlcNAcylation. Unexpectedly, many transcriptional effects of O-GlcNAc transferase (OGT) inhibition were due to the activation of NRF2, the master regulator of redox stress tolerance. Moreover, we found that a signature of low OGT activity strongly correlates with NRF2 activation in multiple tumor expression datasets. Guided by this information, we identified KEAP1 (also known as KLHL19), the primary negative regulator of NRF2, as a direct substrate of OGT We show that O-GlcNAcylation of KEAP1 at serine 104 is required for the efficient ubiquitination and degradation of NRF2. Interestingly, O-GlcNAc levels and NRF2 activation co-vary in response to glucose fluctuations, indicating that KEAP1 O-GlcNAcylation links nutrient sensing to downstream stress resistance. Our results reveal a novel regulatory connection between nutrient-sensitive glycosylation and NRF2 signaling and provide a blueprint for future approaches to discover functionally important O-GlcNAcylation events on other KLHL family proteins in various experimental and disease contexts.
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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.