ArticleJournal of cell science2013
A ligand-specific kinetic switch regulates glucocorticoid receptor trafficking and function.
Article in Journal of cell science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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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.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Unravelling the multifaceted actions of neurosteroids: Machine learning and in vitro screening for novel target discovery.British journal of pharmacology · 2025Article
- Glucocorticoid Insensitivity: Is It a Question of Time and Place?Biomedicines · 2025Review
- Deacylcortivazol-like pyrazole regioisomers reveal a more accommodating expanded binding pocket for the glucocorticoid receptor.RSC medicinal chemistry · 2021Article
- Glucocorticoids rapidly inhibit cell migration through a novel, non-transcriptional HDAC6 pathway.Journal of cell science · 2020Article
- Circadian variation in pulmonary inflammatory responses is independent of rhythmic glucocorticoid signaling in airway epithelial cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Disease- and treatment-associated acquired glucocorticoid resistance.Endocrine connections · 2018Review
- The Role of the Body Clock in Asthma and COPD: Implication for Treatment.Pulmonary therapy · 2018Review
- Glucocorticoid receptor isoforms direct distinct mitochondrial programs to regulate ATP production.Scientific reports · 2016Article
- Coupling of Conformational Transitions in the N-terminal Domain of the 51-kDa FK506-binding Protein (FKBP51) Near Its Site of Interaction with the Steroid Receptor Proteins.The Journal of biological chemistry · 2015Article
- Glucocorticoid receptor regulates accurate chromosome segregation and is associated with malignancy.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Conformational Dynamics in FKBP Domains: Relevance to Molecular Signaling and Drug Design.Current molecular pharmacology · 2015Review
- Differential conformational dynamics in the closely homologous FK506-binding domains of FKBP51 and FKBP52.The Biochemical journal · 2014Article
- The role of glucocorticoid receptor (GR) polymorphisms in human erythropoiesis.American journal of blood research · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The ubiquitously expressed glucocorticoid receptor (GR) is a major drug target for inflammatory disease, but issues of specificity and target tissue sensitivity remain. We now identify high potency, non-steroidal GR ligands, GSK47867A and GSK47869A, which induce a novel conformation of the GR ligand-binding domain (LBD) and augment the efficacy of cellular action. Despite their high potency, GSK47867A and GSK47869A both induce surprisingly slow GR nuclear translocation, followed by prolonged nuclear GR retention, and transcriptional activity following washout. We reveal that GSK47867A and GSK47869A specifically alter the GR LBD structure at the HSP90-binding site. The alteration in the HSP90-binding site was accompanied by resistance to HSP90 antagonism, with persisting transactivation seen after geldanamycin treatment. Taken together, our studies reveal a new mechanism governing GR intracellular trafficking regulated by ligand binding that relies on a specific surface charge patch within the LBD. This conformational change permits extended GR action, probably because of altered GR-HSP90 interaction. This chemical series may offer anti-inflammatory drugs with prolonged duration of action due to altered pharmacodynamics rather than altered pharmacokinetics.
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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.