ArticleCell chemical biology2023
Succinylation of a KEAP1 sensor lysine promotes NRF2 activation.
Article in Cell chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 27 citations in OpenAlex.
- Crosstalk between cysteine and lysine modifications: Integrating redox and metabolic regulation.Redox biology · 2026Review
- Crosstalk Between Nrf2 and Metabolic Pathways: Redox Regulation, Glutaminolysis, and Cellular Proliferation.Cell biochemistry and biophysics · 2026Review
- Bone marrow stromal cells promote chemoresistance in acute myeloid leukaemia through P2RX7-mediated antioxidant defence.Experimental & molecular medicine · 2026Article
- Genipin induces liver injury by disrupting the CPS1-regulated urea cycle and redox homeostasis.Journal of pharmaceutical analysis · 2026Article
- Cancer-associated adipocytes: metabolic reprogramming, crosstalk and therapeutic implications in tumor progression.Signal transduction and targeted therapy · 2026Review
- Molecular Mechanisms of Cadmium-Induced Apoptosis in Fish Cells: A Review.International journal of molecular sciences · 2026Review
- β-Hydroxybutyrate Attenuates Diabetic Kidney Disease Partially Via β-hydroxybutyrylation of Nrf2.Inflammation · 2026Article
- Ginsenoside Rb1 alleviates overtraining-induced oxidative stress in mouse liver by stimulating mitophagy via Nrf2 pathway.Frontiers in nutrition · 2026Article
- The Central Role of NRF2 in Cancer Metabolism and Redox Signaling: Novel Insights into Crosstalk with ER Stress and Therapeutic Modulation.Cell biochemistry and biophysics · 2025Review
- Post-translational acylation of proteins in cardiac hypertrophy.Nature reviews. Cardiology · 2025Review
- Post-translational modifications regulating microglial inflammation in central nervous system disorders: a review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- GCLC desuccinylation regulated by oxidative stress protects human cancer cells from ferroptosis.Cell death and differentiation · 2025Article
- Serpina3c deficiency promotes obesity-related hypertriglyceridemia and inflammation through activation of the Hif1α-glycolysis axis in adipose tissue.Clinical science (London, England : 1979) · 2025Article
- Acyl post-translational modification of proteins by metabolites in cancer cells.Cell death discovery · 2025Review
- Stressing out with electrophiles.Nature chemical biology · 2025Article
- SIRT7-mediated NRF2 deacetylation promotes antioxidant response and protects against chemodrug-induced liver injury.Cell death & disease · 2025Article
- HPPE Activates NRF2 Signaling by Liberating Heavy Metal Stores.Chembiochem : a European journal of chemical biology · 2025Article
- The glycolytic metabolite methylglyoxal covalently inactivates the NLRP3 inflammasome.Cell reports · 2024Article
- Succinylation of Park7 activates a protective metabolic response to acute kidney injury.American journal of physiology. Renal physiology · 2024Article
- Mapping stress-responsive signaling pathways induced by mitochondrial proteostasis perturbations.Molecular biology of the cell · 2024Article
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9 authors at 2 institutions in 1 country.
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Abstract
Cross talk between metabolism and stress-responsive signaling is essential for maintaining cellular homeostasis. This cross talk is often achieved through covalent modification of proteins by endogenous, reactive metabolites that regulate key stress-responsive transcription factors like NRF2. Metabolites including methylglyoxal, glyceraldehyde 3-phosphate, fumarate, and itaconate covalently modify sensor cysteines of the NRF2 repressor KEAP1, resulting in stabilization of NRF2 and activation of its cytoprotective transcriptional program. Here, we employed a shRNA-based screen targeting the enzymes of central carbon metabolism to identify additional regulatory nodes bridging metabolism to NRF2 activation. Succinic anhydride, increased by genetic depletion of the TCA cycle enzyme succinyl-CoA synthetase or by direct administration, results in N-succinylation of lysine 131 of KEAP1 to activate NRF2 signaling. This study identifies KEAP1 as capable of sensing reactive metabolites not only by several cysteine residues but also by a conserved lysine residue, indicating its potential to sense an expanded repertoire of reactive metabolic messengers.
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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.