ArticleInvestigative ophthalmology & visual science2008
FK506-binding protein 51 regulates nuclear transport of the glucocorticoid receptor beta and glucocorticoid responsiveness.
Article in Investigative ophthalmology & visual science, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.
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Who cites it
51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 119 citations in OpenAlex.
- Epigenetic Pathways in Human Disease: The Impact of DNA Methylation on Stress-Related Pathogenesis and Current Challenges in Biomarker Development.EBioMedicine · 2017Pooled it
- Common variants in FKBP5 gene and major depressive disorder (MDD) susceptibility: a comprehensive meta-analysis.Scientific reports · 2016Pooled it
- FKBP5 polymorphisms and antidepressant response in geriatric depression.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2010Trial
- Time-Dependent Glucocorticoid-Induced Transcriptomic Changes in Human Trabecular Meshwork and Schlemm's Canal Cells.Investigative ophthalmology & visual science · 2026Article
- Time-dependent Glucocorticoid-Induced Transcriptomic Changes in Human Trabecular Meshwork and Schlemm's Canal.bioRxiv : the preprint server for biology · 2026Article
- Epigenetics of glaucoma in the trabecular meshwork.Clinical epigenetics · 2025Review
- Lithium Treatment Increases FKBP5 Protein but Not mRNA Expression in the Pituitary Gland of Depressive-like Rats.Brain sciences · 2025Article
- The rs1360780 Variant ofGenes · 2025Review
- Exploring the role of glucocorticoid receptors and co-chaperones in Pemphigus foliaceus stratification.Archives of dermatological research · 2025Article
- The relationship between the intraocular position of dexamethasone intravitreal implant and post-injection intraocular pressure elevation.Frontiers in medicine · 2025Article
- Article
- Glucocorticoid-Induced Ocular Hypertension and Glaucoma.Clinical ophthalmology (Auckland, N.Z.) · 2024Review
- Dexamethasone Intravitreal Implant Is Active at the Molecular Level Eight Weeks after Implantation in Experimental Central Retinal Vein Occlusion.Molecules (Basel, Switzerland) · 2022Article
- Article
- FKBP51 and the molecular chaperoning of metabolism.Trends in endocrinology and metabolism: TEM · 2021Review
- Experience and activity-dependent control of glucocorticoid receptors during the stress response in large-scale brain networks.Stress (Amsterdam, Netherlands) · 2021Article
- Intraocular pressure fluctuation following intravitreal dexamethasone implant and incidence of secondary ocular hypertension: a Zambian perspective.The Pan African medical journal · 2021Article
- NGS study of glucocorticoid response genes in inflammatory bowel disease patients.Archives of medical science : AMS · 2021Article
- The glucocorticoid receptor-FKBP51 complex contributes to fear conditioning and posttraumatic stress disorder.The Journal of clinical investigation · 2020Article
- Longitudinal detection of retinal alterations by visible and near-infrared optical coherence tomography in a dexamethasone-induced ocular hypertension mouse model.Neurophotonics · 2019Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
purposeA spliced variant of the human glucocorticoid receptor GRbeta has been implicated in glucocorticoid responsiveness in glaucoma. Over-expression of the FK506-binding immunophilin FKBP51 also causes a generalized state of glucocorticoid resistance. In the present study, the roles of FKBP51 in the nuclear transport of GRbeta and glucocorticoid responsiveness were investigated.
methodsHuman trabecular meshwork cells (GTM3 and TM5) and HeLa cells were treated with dexamethasone (DEX) and FK506 and transfected with GRbeta and FKBP51 expression vectors. Coimmunoprecipitation and Western blot analyses were performed to study interactions of FKBP51 and FKBP52 with GRalpha, GRbeta, Hsp90, or dynein. The cells were transfected with a GRE-luciferase reporter to evaluate the effects of DEX and FK506 and the overexpression of GRbeta and FKBP51 on glucocorticoid-mediated gene expression.
resultsFKBP51 was involved in constitutive nuclear transport of both GRalpha and -beta in the absence of ligands. FKBP52 appeared to be solely responsible for the nuclear transport of ligand-activated GRalpha. DEX stimulated the translocation of GRalpha but not GRbeta. Overexpression of either GRbeta or FKBP51 stimulated GRbeta translocation and reduced DEX-induced luciferase in HeLa cells. FK506 did not alter DEX-induced translocation of GRalpha. However, FK506 increased the association of FKBP51 with GRbeta and stimulated DEX-induced translocation of GRbeta in normal TM cells, but not in glaucoma TM cells. Increased nuclear GRbeta significantly inhibited glucocorticoid responsiveness in TM cells.
conclusionsNuclear transport of GRbeta represents a novel mechanism through which FKBP51 alters GC sensitivity. GRbeta and FKBP51 may be responsible for increased responsiveness in steroid-induced ocular hypertensive individuals as well as in patients with glaucoma.
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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.