ArticleCell death and differentiation2016
The activity of the glucocorticoid receptor is regulated by SUMO conjugation to FKBP51.
Article in Cell death and differentiation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- From Biomarkers to New Treatments for Post-Traumatic Stress Disorder.Neuroscience bulletin · 2026Review
- FKBP5 regulates interferon signaling leading to myeloid cell activation in multiple sclerosis.Journal of neuroinflammation · 2026Article
- Increased HSD11β1 Expression in Human Leiomyomatous Uteri: Implication for Enhanced Glucocorticoid Signaling.The Journal of clinical endocrinology and metabolism · 2025Article
- Targeting glucocorticoid receptor signaling pathway for treatment of stress-related brain disorders.Pharmacological reports : PR · 2024Review
- Impact of Co-chaperones and Posttranslational Modifications Toward Hsp90 Drug Sensitivity.Sub-cellular biochemistry · 2023Article
- Tricyclic antidepressants target FKBP51 SUMOylation to restore glucocorticoid receptor activity.Molecular psychiatry · 2022Article
- Post-translational modifications and stress adaptation: the paradigm of FKBP51.Biochemical Society transactions · 2020Review
- Evidence of increased hypoxia signaling in fetal liver from maternal nutrient restriction in mice.Pediatric research · 2020Article
- The Many Faces of FKBP51.Biomolecules · 2019Review
- Stress, alcohol and infection during early development: A brief review of common outcomes and mechanisms.Journal of neuroendocrinology · 2018Review
- Relationship Between Homodimeric Glucocorticoid Receptor and Transcriptional Regulation Assessed via an In Vitro Fluorescence Correlation Spectroscopy-Microwell System.Scientific reports · 2018Article
- Regulatory and Mechanistic Actions of Glucocorticoids on T and Inflammatory Cells.Frontiers in endocrinology · 2018Review
- The FKBP51 Glucocorticoid Receptor Co-Chaperone: Regulation, Function, and Implications in Health and Disease.International journal of molecular sciences · 2017Review
- Glucocorticoid receptors: finding the middle ground.The Journal of clinical investigation · 2017Review
- A comprehensive platform for the analysis of ubiquitin-like protein modifications using in vivo biotinylation.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
FK506-binding protein 51 (FKBP51) regulates the activity of the glucocorticoid receptor (GR), and is therefore a key mediator of the biological actions of glucocorticoids. However, the understanding of the molecular mechanisms that govern its activity remains limited. Here, we uncover a novel regulatory switch for GR activity by the post-translational modification of FKBP51 with small ubiquitin-like modifier (SUMO). The major SUMO-attachment site, lysine 422, is required for FKBP51-mediated inhibition of GR activity in hippocampal neuronal cells. Importantly, impairment of SUMO conjugation to FKBP51 impacts on GR-dependent neuronal signaling and differentiation. We demonstrate that SUMO conjugation to FKBP51 is enhanced by the E3 ligase PIAS4 and by environmental stresses such as heat shock, which impact on GR-dependent transcription. SUMO conjugation to FKBP51 regulates GR hormone-binding affinity and nuclear translocation by promoting FKBP51 interaction within the GR complex. SUMOylation-deficient FKBP51 fails to interact with Hsp90 and GR thus facilitating the recruitment of the closely related protein, FKBP52, which enhances GR transcriptional activity. Moreover, we show that the modification of FKBP51 with SUMO modulates its binding to Hsp90. Our data establish SUMO conjugation as a novel regulatory mechanism in the Hsp90 cochaperone activity of FKBP51 with a functional impact on GR signaling in a neuronal context.
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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.