ArticleGenes & development2000
The glucocorticoid receptor inhibits NFkappaB by interfering with serine-2 phosphorylation of the RNA polymerase II carboxy-terminal domain.
Article in Genes & development, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 186 papers.
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186 citing papers in PubMed, 554 citations in OpenAlex.
- Balancing inflammation under stress: glucocorticoid regulation of innate immune pathways.Bioscience reports · 2026Review
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- ChIP happens: from biochemical origins to the modern omics toolbox for understanding steroid hormone receptors.The Biochemical journal · 2026Review
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- Cardiomyocyte Glucocorticoid Receptors Exacerbate Stress Effects in Myocardial Ischemia Injury in Mice.Cells · 2025Article
- The Binding Landscape of an Essential Nuclear Hormone Receptor inbioRxiv : the preprint server for biology · 2025Article
- Transcriptional pause release at enhancers mediates cell identity.NAR cancer · 2025Review
- Beyond Fluid Therapy: The Role of Vitamin C, Steroids, and Thiamine in Sepsis Management.Cureus · 2025Review
- Improving data interpretability with new differential sample variance gene set tests.BMC bioinformatics · 2025Article
- Reactivation of latent HIV-1 by the glucocorticoid receptor modulator AZD9567.Journal of virology · 2025Article
- Functional characterization of eQTLs and asthma risk loci with scATAC-seq across immune cell types and contexts.American journal of human genetics · 2025Article
- The Bidirectional Interaction Between NF-Journal of immunology research · 2025Review
- DFF-ChIP: a method to detect and quantify complex interactions between RNA polymerase II, transcription factors, and chromatin.Nucleic acids research · 2024Article
- Glucocorticoids Suppress NF-κB-Mediated Neutrophil Control of Aspergillus fumigatus Hyphal Growth.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Possible Role of NRF2 in Cell Response to OZOILE (Stable Ozonides) in Children Affected by Lichen Sclerosus of Foreskin.Current issues in molecular biology · 2024Article
- Article
- Review
- Crosstalk between glucocorticoid and mineralocorticoid receptors boosts glucocorticoid-induced killing of multiple myeloma cells.Cellular and molecular life sciences : CMLS · 2023Article
- Glucocorticoid Treatment in Acute Respiratory Distress Syndrome: An Overview on Mechanistic Insights and Clinical Benefit.International journal of molecular sciences · 2023Review
- The role of O-GlcNAcylation in innate immunity and inflammation.Journal of molecular cell biology · 2023Review
126 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucocorticoids repress NFkappaB-mediated activation of proinflammatory genes such as interleukin-8 (IL-8) and ICAM-1. Our experiments suggest that the glucocorticoid receptor (GR) confers this effect by associating through protein-protein interactions with NFkappaB bound at each of these genes. That is, we show that the GR zinc binding region (ZBR), which includes the DNA binding and dimerization functions of the receptor, binds directly to the dimerization domain of the RelA subunit of NFkappaB in vitro and that the ZBR is sufficient to associate with RelA bound at NFkappaB response elements in vivo. Moreover, we demonstrate in vivo and in vitro that GR does not disrupt DNA binding by NFkappaB. In transient transfections, we found that the GR ligand binding domain is essential for repression of NFkappaB but not for association with it and that GR can repress an NFkappaB derivative bearing a heterologous activation domain. We used chromatin immunoprecipitation assays in untransfected A549 cells to infer the mechanism by which the tethered GR represses NFkappaB-activated transcription. As expected, we found that the inflammatory signal TNFalpha stimulated preinitiation complex (PIC) assembly at the IL-8 and ICAM-1 promoters and that the largest subunit of RNA polymerase II (pol II) in those complexes became phosphorylated at serines 2 and 5 in its carboxy-terminal domain (CTD) heptapeptide repeats (YSPTSPS); these modifications are required for transcription initiation. Remarkably, GR did not inhibit PIC assembly under repressing conditions, but rather interfered with phosphorylation of serine 2 of the pol II CTD.
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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.