ArticleJournal of the American Chemical Society2015
Substoichiometric hydroxynonenylation of a single protein recapitulates whole-cell-stimulated antioxidant response.
Article in Journal of the American Chemical Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Keeping Wavering Bonds: Deactivation-Induced Signaling by Reactive Electrophiles.Biochemistry · 2026Review
- EGFR inhibitor-resistant lung cancers exhibit collateral sensitivity to a covalent, cysteine-independent KEAP1 oligomerizing molecular bridge.Nature communications · 2026Article
- CO-resistant hydrogenation over noble metal/α-MoC catalyst.Nature communications · 2025Article
- The master antioxidant defense is activated during EBV latent infection.Journal of virology · 2023Article
- Nucleophilic covalent ligand discovery for the cysteine redoxome.Nature chemical biology · 2023Article
- Z-REX: shepherding reactive electrophiles to specific proteins expressed tissue specifically or ubiquitously, and recording the resultant functional electrophile-induced redox responses in larval fish.Nature protocols · 2023Review
- The 4-Hydroxynonenal-Protein Adducts and Their Biological Relevance: Are Some Proteins Preferred Targets?Antioxidants (Basel, Switzerland) · 2023Review
- Finding a vocation for validation: taking proteomics beyond association and location.RSC chemical biology · 2023Review
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- A chemical tool for blue light-inducible proximity photo-crosslinking in live cells.Chemical science · 2022Article
- A primer on harnessing non-enzymatic post-translational modifications for drug design.RSC medicinal chemistry · 2021Article
- Wdr1 and cofilin are necessary mediators of immune-cell-specific apoptosis triggered by Tecfidera.Nature communications · 2021Article
- Getting the Right Grip? How Understanding Electrophile Selectivity Profiles Could Illuminate Our Understanding of Redox Signaling.Antioxidants & redox signaling · 2020Article
- An Untargeted Approach for Revealing Electrophilic Metabolites.ACS chemical biology · 2020Article
- Visualizing and Manipulating Biological Processes by Using HaloTag and SNAP-Tag Technologies.Chembiochem : a European journal of chemical biology · 2020Review
- Neighborhood watch: tools for defining locale-dependent subproteomes and their contextual signaling activities.RSC chemical biology · 2020Review
- The mRNA-Binding Protein HuR Is a Kinetically-Privileged Electrophile Sensor.Helvetica chimica acta · 2020Article
- REX technologies for profiling and decoding the electrophile signaling axes mediated by Rosetta Stone proteins.Methods in enzymology · 2020Article
- Electrophile Signaling and Emerging Immuno- and Neuro-modulatory Electrophilic Pharmaceuticals.Frontiers in aging neuroscience · 2020Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Lipid-derived electrophiles (LDEs) that can directly modify proteins have emerged as important small-molecule cues in cellular decision-making. However, because these diffusible LDEs can modify many targets [e.g., >700 cysteines are modified by the well-known LDE 4-hydroxynonenal (HNE)], establishing the functional consequences of LDE modification on individual targets remains devilishly difficult. Whether LDE modifications on a single protein are biologically sufficient to activate discrete redox signaling response downstream also remains untested. Herein, using T-REX (targetable reactive electrophiles and oxidants), an approach aimed at selectively flipping a single redox switch in cells at a precise time, we show that a modest level (∼34%) of HNEylation on a single target is sufficient to elicit the pharmaceutically important antioxidant response element (ARE) activation, and the resultant strength of ARE induction recapitulates that observed from whole-cell electrophilic perturbation. These data provide the first evidence that single-target LDE modifications are important individual events in mammalian physiology.
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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.