ArticleJournal of the American Chemical Society2015
A generalizable platform for interrogating target- and signal-specific consequences of electrophilic modifications in redox-dependent cell signaling.
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 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 71 citations in OpenAlex.
- Keeping Wavering Bonds: Deactivation-Induced Signaling by Reactive Electrophiles.Biochemistry · 2026Review
- Identification of Methylglyoxal Reactive Proteins with Photocaged Glycating Agents.Chembiochem : a European journal of chemical biology · 2025Article
- Toward decoding spatiotemporal signaling activities of reactive immunometabolites with precision immuno-chemical biology tools.Communications chemistry · 2024Review
- 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
- Article
- Role of Protein Damage Inflicted by Dopamine Metabolites in Parkinson's Disease: Evidence, Tools, and Outlook.Chemical research in toxicology · 2022Review
- Molecular probes for cellular imaging of post-translational proteoforms.RSC chemical biology · 2022Review
- Function-guided proximity mapping unveils electrophilic-metabolite sensing by proteins not present in their canonical locales.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Photocaged dicarbonyl probe provides spatiotemporal control over protein glycation.Chemical communications (Cambridge, England) · 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
- Synthesis and evaluation of porphyrin glycoconjugates varying in linker length: preliminary effects on the photodynamic inactivation ofRSC advances · 2021Article
- Getting the Right Grip? How Understanding Electrophile Selectivity Profiles Could Illuminate Our Understanding of Redox Signaling.Antioxidants & redox signaling · 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
- Genie in a bottle: controlled release helps tame natural polypharmacology?Current opinion in chemical biology · 2019Review
- Chemical Biology Gateways to Mapping Location, Association, and Pathway Responsivity.Frontiers in chemistry · 2019Review
- Proteomics and Beyond: Cell Decision-Making Shaped by Reactive Electrophiles.Trends in biochemical sciences · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Despite the known propensity of small-molecule electrophiles to react with numerous cysteine-active proteins, biological actions of individual signal inducers have emerged to be chemotype-specific. To pinpoint and quantify the impacts of modifying one target out of the whole proteome, we develop a target-protein-personalized "electrophile toolbox" with which specific intracellular targets can be selectively modified at a precise time by specific reactive signals. This general methodology, T-REX (targetable reactive electrophiles and oxidants), is established by (1) constructing a platform that can deliver a range of electronic and sterically different bioactive lipid-derived signaling electrophiles to specific proteins in cells; (2) probing the kinetics of targeted delivery concept, which revealed that targeting efficiency in cells is largely driven by initial on-rate of alkylation; and (3) evaluating the consequences of protein-target- and small-molecule-signal-specific modifications on the strength of downstream signaling. These data show that T-REX allows quantitative interrogations into the extent to which the Nrf2 transcription factor-dependent antioxidant response element (ARE) signaling is activated by selective electrophilic modifications on Keap1 protein, one of several redox-sensitive regulators of the Nrf2-ARE axis. The results document Keap1 as a promiscuous electrophile-responsive sensor able to respond with similar efficiencies to discrete electrophilic signals, promoting comparable strength of Nrf2-ARE induction. T-REX is also able to elicit cell activation in cases in which whole-cell electrophile flooding fails to stimulate ARE induction prior to causing cytotoxicity. The platform presents a previously unavailable opportunity to elucidate the functional consequences of small-molecule-signal- and protein-target-specific electrophilic modifications in an otherwise unaffected cellular background.
Indexed as
Identifiers
What OpenQuestion holds
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.