ArticleThe Journal of steroid biochemistry and molecular biology2009
Targeted ablation reveals a novel role of FKBP52 in gene-specific regulation of glucocorticoid receptor transcriptional activity.
Article in The Journal of steroid biochemistry and molecular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Glucocorticoid resistance-induced inflammation drives cardiovascular-kidney-metabolic (CKM) syndrome pathophysiology.Trends in endocrinology and metabolism: TEM · 2026Review
- Targeting the Gut-Brain Axis Through Insulin-like Growth Factors: Therapeutic Implications and Future Directions.Journal of molecular neuroscience : MN · 2025Review
- The physiology of MASLD: molecular pathways between liver and adipose tissues.Clinical science (London, England : 1979) · 2025Review
- Glucocorticoid resistance remodels liver lipids and prompts lipogenesis, eicosanoid, and inflammatory pathways.Prostaglandins & other lipid mediators · 2024Review
- Glucocorticoids, their uses, sexual dimorphisms, and diseases: new concepts, mechanisms, and discoveries.Physiological reviews · 2024Review
- Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the glucocorticoid receptor.Nature structural & molecular biology · 2023Article
- Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the Glucocorticoid Receptor.bioRxiv : the preprint server for biology · 2023Article
- Differential Effects of Fkbp4 and Fkbp5 on Regulation of theInternational journal of molecular sciences · 2021Article
- FKBP52 overexpression accelerates hippocampal-dependent memory impairments in a tau transgenic mouse model.NPJ aging and mechanisms of disease · 2021Article
- Hsp90 Heterocomplexes Regulate Steroid Hormone Receptors: From Stress Response to Psychiatric Disease.International journal of molecular sciences · 2018Review
- Male-specific effects of lipopolysaccharide on glucocorticoid receptor nuclear translocation in the prefrontal cortex of depressive rats.Psychopharmacology · 2016Article
- Timcodar (VX-853) Is a Non-FKBP12 Binding Macrolide Derivative That Inhibits PPARγ and Suppresses Adipogenesis.PPAR research · 2016Article
- Pharmacological stimulation of hypoxia inducible factor-1α facilitates the corticosterone response to a mild acute stressor.Neuroscience letters · 2015Article
- FK506-Binding Proteins and Their Diverse Functions.Current molecular pharmacology · 2015Review
- Analysis of FK506, timcodar (VX-853) and FKBP51 and FKBP52 chaperones in control of glucocorticoid receptor activity and phosphorylation.Pharmacology research & perspectives · 2014Article
- FKBP51 reciprocally regulates GRα and PPARγ activation via the Akt-p38 pathway.Molecular endocrinology (Baltimore, Md.) · 2014Article
- Control of steroid receptor dynamics and function by genomic actions of the cochaperones p23 and Bag-1L.Nuclear receptor signaling · 2014Review
- The HPA - Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain.Frontiers in immunology · 2014Review
- Functional diversity and pharmacological profiles of the FKBPs and their complexes with small natural ligands.Cellular and molecular life sciences : CMLS · 2013Review
- The helix 1-3 loop in the glucocorticoid receptor LBD is a regulatory element for FKBP cochaperones.Molecular endocrinology (Baltimore, Md.) · 2013Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
FKBP52 is a tetratricopeptide repeat (TPR) protein with peptidyl-prolyl isomerase activity and is found in steroid receptor complexes, including glucocorticoid receptor (GR). It is generally accepted that FKBP52 has a stimulatory effect on GR transcriptional activity. However, the mechanism by which FKBP52 controls GR is not yet clear, with reports showing effects on GR hormone-binding affinity and/or hormone-induced nuclear translocation. To address this issue, we have generated mice with targeted ablation of the FKBP52 gene. To date, no overt defects of GR-regulated physiology have been found in these animals, demonstrating that FKBP52 is not an essential regulator of global GR activity. To better assess the impact of FKBP52 on GR, mouse embryonic fibroblasts (MEFs) were generated from wild-type (WT) and FKBP52-deficient (KO) animals. Analysis of GR activity at reporter genes showed an approximate 70% reduction of activity in 52KO MEF cells, with no effect of FKBP52 loss on thyroid receptor. Interestingly, GR activity at endogenous genes was not globally affected in 52KO cells, with reduced activity at GILZ and FKBP51, but not at SGK and p21. Thus, FKBP52 appears to be a gene-specific modulator of GR. To investigate the mechanism of this action, analyses of GR heterocomplex composition, hormone-binding affinity, and ability to undergo hormone-induced nuclear translocation and DNA-binding were performed. Interestingly, no effect of FKBP52 loss was found for any of these GR properties, suggesting that the main function of FKBP52 is a heretofore-unknown ability to control GR activity at target genes. Lastly, loss of FKBP52 did not affect the ability of GR to undergo hormone-induced autologous down-regulation, showing that FKBP52 does not contribute to all branches of GR signaling. The implications of these results to the potential actions of FKBP52 on GR activity in vivo are discussed.
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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.