ArticleMolecular and cellular biology2016
A Novel Allosteric Mechanism of NF-κB Dimerization and DNA Binding Targeted by an Anti-Inflammatory Drug.
Article in Molecular and cellular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
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- Inhibitors of eIF4G1-eIF1 uncover its regulatory role of ER/UPR stress-response genes independent of eIF2α-phosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Anti-Inflammatory Extract from Soil AlgaeCells · 2022Article
- Protein-fragment complementation assays for large-scale analysis of protein-protein interactions.Biochemical Society transactions · 2021Review
- Fluorescent thermal shift-based method for detection of NF-κB binding to double-stranded DNA.Scientific reports · 2021Article
- Tackling Chronic Inflammation with Withanolide Phytochemicals-A Withaferin a Perspective.Antioxidants (Basel, Switzerland) · 2020Review
- Broad-spectrum antitumor properties of Withaferin A: a proteomic perspective.RSC medicinal chemistry · 2020Review
- Prenatal epigenetics diets play protective roles against environmental pollution.Clinical epigenetics · 2019Review
- Assaying Homodimers of NF-κB in Live Single Cells.Frontiers in immunology · 2019Article
- Dynamic Interaction of Eukaryotic Initiation Factor 4G1 (eIF4G1) with eIF4E and eIF1 Underlies Scanning-Dependent and -Independent Translation.Molecular and cellular biology · 2018Article
- Precision engineering of targeted nanocarriers.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2018Review
- Efficient and Accurate Translation Initiation Directed by TISU Involves RPS3 and RPS10e Binding and Differential Eukaryotic Initiation Factor 1A Regulation.Molecular and cellular biology · 2017Article
- Withania somnifera and Its Withanolides Attenuate Oxidative and Inflammatory Responses and Up-Regulate Antioxidant Responses in BV-2 Microglial Cells.Neuromolecular medicine · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The NF-κB family plays key roles in immune and stress responses, and its deregulation contributes to several diseases. Therefore its modulation has become an important therapeutic target. Here, we used a high-throughput screen for small molecules that directly inhibit dimerization of the NF-κB protein p65. One of the identified inhibitors is withaferin A (WFA), a documented anticancer and anti-inflammatory compound. Computational modeling suggests that WFA contacts the dimerization interface on one subunit and surface residues E285 and Q287 on the other. Despite their locations far from the dimerization site, E285 and Q287 substitutions diminished both dimerization and the WFA effect. Further investigation revealed that their effects on dimerization are associated with their proximity to a conserved hydrophobic core domain (HCD) that is crucial for dimerization and DNA binding. Our findings established NF-κB dimerization as a drug target and uncovered an allosteric domain as a target of WFA action.
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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.