ArticleScientific reports2018
Novel role for receptor dimerization in post-translational processing and turnover of the GRα.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- How post-translational modifications impact glucocorticoid receptor function in human pathologies.Cell communication and signaling : CCS · 2026Review
- Glucocorticoid Receptor and SUMO Fluctuations in Response to Pulsatile Glucocorticoids In Vitro and in Male Rat Brains.Endocrinology · 2025Article
- Oncogenic Activity of Glucocorticoid Receptor β Is Controlled by Ubiquitination-Dependent Interaction with USP49 in Glioblastoma Cells.Molecular cancer research : MCR · 2022Article
- Review
- Glutamine synthetase regulation by dexamethasone, RU486, and compound A in astrocytes derived from aged mouse cerebral hemispheres is mediated via glucocorticoid receptor.Molecular and cellular biochemistry · 2021Article
- Review
- Limitations to intergenerational inheritance: subchronic paternal stress preconception does not influence offspring anxiety.Scientific reports · 2020Article
- Therapeutic glucocorticoids: mechanisms of actions in rheumatic diseases.Nature reviews. Rheumatology · 2020Review
- Multifaceted Control of GR Signaling and Its Impact on Hepatic Transcriptional Networks and Metabolism.Frontiers in endocrinology · 2020Review
- GR Dimerization and the Impact of GR Dimerization on GR Protein Stability and Half-Life.Frontiers in immunology · 2019Review
- A General Introduction to Glucocorticoid Biology.Frontiers in immunology · 2019Review
- Disease- and treatment-associated acquired glucocorticoid resistance.Endocrine connections · 2018Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Glucocorticoids (GCs), acting via the glucocorticoid receptor (GRα), remain the mainstay therapeutic choice for the treatment of inflammation. However, chronic GC use, aside from generating undesirable side-effects, results in GRα down-regulation, often coupled to a decrease in GC-responsiveness, which may culminate in acquired GC resistance. The current study presents evidence for a novel role of the dimerization state of the GRα in mediating GC-mediated GRα turnover. Through comparing the effects of dimerization promoting GCs on down-regulation of a transfected human wild type GRα (hGRwt) or a dimerization deficient GRα mutant (hGRdim), we established that a loss of receptor dimerization restricts GRα turnover, which was supported by the use of the dimerization abrogating Compound A (CpdA), in cells containing endogenous GRα. Moreover, we showed that the dimerization state of the GRα influenced the post-translational processing of the receptor, specifically hyper-phosphorylation at Ser404, which influenced the interaction of GRα with the E3 ligase, FBXW7α, thus hampering receptor turnover via the proteasome. Lastly, the restorative effects of CpdA on the GRα pool, in the presence of Dex, were demonstrated in a combinatorial treatment protocol. These results expand our understanding of factors that contribute to GC-resistance and may be exploited clinically.
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