Cofactor Profiling of the Glucocorticoid Receptor from a Cellular Environment

Desmet, Sofie; Dejager, Lien; Clarisse, Dorien; Thommis, Jonathan; Melchers, Diana; Bastiaensen, Niek; Ruijtenbeek, Rob; Beck, Ilse; Libert, Claude; Meijer, Onno C.; Bosscher, Karolien De

doi:10.1007/978-1-4939-1346-6_8

Cited by 20 publications

(21 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ATAC-seq approach is very promising, as it can already at this stage probe general chromatin accessibility in as little as 500 neurons (Buenrostro et al 2013 ). Large-scale profiling of in vivo protein interaction is possible for particular sets of interactions, such as the coregulators that interact with the GR AF-2 (Desmet et al 2014 ), and in open approaches (Lempiäinen et al 2017 ).…”

Section: Factors Modifying Genomic Activitymentioning

confidence: 99%

Corticosteroid Receptors in the Brain: Transcriptional Mechanisms for Specificity and Context-Dependent Effects

2018

Self Cite

View full text Add to dashboard Cite

Corticosteroid hormones act in the brain to support adaptation to stress via binding to mineralocorticoid and glucocorticoid receptors (MR and GR). These receptors act in large measure as transcription factors. Corticosteroid effects can be highly divergent, depending on the receptor type, but also on brain region, cell type, and physiological context. These differences ultimately depend on differential interactions of MR and GR with other proteins, which determine ligand binding, nuclear translocation, and transcriptional activities. In this review, we discuss established and potential mechanisms that confer receptor and cell type-specific effects of the MR and GR-mediated transcriptional effects in the brain.

show abstract

Section: Factors Modifying Genomic Activitymentioning

confidence: 99%

Corticosteroid Receptors in the Brain: Transcriptional Mechanisms for Specificity and Context-Dependent Effects

2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…The effect on transcription depends on binding to DNA and/or other transcription factors and on the recruitment of GR coregulators. The latter proteins include coactivators and corepressors that assist in GR transcriptional activity (66). …”

Section: Glucocorticoids (Gcs) and The Glucocorticoid Receptor (Gr)mentioning

confidence: 99%

Endothelial Response to Glucocorticoids in Inflammatory Diseases

et al. 2016

Self Cite

View full text Add to dashboard Cite

The endothelium plays a crucial role in inflammation. A balanced control of inflammation requires the action of glucocorticoids (GCs), steroidal hormones with potent cell-specific anti-inflammatory properties. Besides the classic anti-inflammatory effects of GCs on leukocytes, recent studies confirm that endothelial cells also represent an important target for GCs. GCs regulate different aspects of endothelial physiology including expression of adhesion molecules, production of pro-inflammatory cytokines and chemokines, and maintenance of endothelial barrier integrity. However, the regulation of endothelial GC sensitivity remains incompletely understood. In this review, we specifically examine the endothelial response to GCs in various inflammatory diseases ranging from multiple sclerosis, stroke, sepsis, and vasculitis to atherosclerosis. Shedding more light on the cross talk between GCs and endothelium will help to improve existing therapeutic strategies and develop new therapies better tailored to the needs of patients.

show abstract

“…Co-regulator recruitment by GR on binding 20β-DHF was assessed by microarray assay for real-time co-regulator-nuclear receptor interaction (MARCoNI) with the GR agonist dexamethasone used as a positive control 25 . Under these conditions, 20β-DHF-activated GR recruited approximately 36% of the co-regulators recruited by dexamethasone (Fig.…”

Section: Resultsmentioning

confidence: 99%

Carbonyl reductase 1 catalyzes 20β-reduction of glucocorticoids, modulating receptor activation and metabolic complications of obesity

Morgan

Beck

Nixon

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

Carbonyl Reductase 1 (CBR1) is a ubiquitously expressed cytosolic enzyme important in exogenous drug metabolism but the physiological function of which is unknown. Here, we describe a role for CBR1 in metabolism of glucocorticoids. CBR1 catalyzes the NADPH- dependent production of 20β-dihydrocortisol (20β-DHF) from cortisol. CBR1 provides the major route of cortisol metabolism in horses and is up-regulated in adipose tissue in obesity in horses, humans and mice. We demonstrate that 20β-DHF is a weak endogenous agonist of the human glucocorticoid receptor (GR). Pharmacological inhibition of CBR1 in diet-induced obesity in mice results in more marked glucose intolerance with evidence for enhanced hepatic GR signaling. These findings suggest that CBR1 generating 20β-dihydrocortisol is a novel pathway modulating GR activation and providing enzymatic protection against excessive GR activation in obesity.

show abstract

Cofactor Profiling of the Glucocorticoid Receptor from a Cellular Environment

Cited by 20 publications

References 4 publications

Corticosteroid Receptors in the Brain: Transcriptional Mechanisms for Specificity and Context-Dependent Effects

Corticosteroid Receptors in the Brain: Transcriptional Mechanisms for Specificity and Context-Dependent Effects

Endothelial Response to Glucocorticoids in Inflammatory Diseases

Carbonyl reductase 1 catalyzes 20β-reduction of glucocorticoids, modulating receptor activation and metabolic complications of obesity

Contact Info

Product

Resources

About