ArticleSteroids2010
Lysine 419 targets human glucocorticoid receptor for proteasomal degradation.
Article in Steroids, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 51 citations in OpenAlex.
- How post-translational modifications impact glucocorticoid receptor function in human pathologies.Cell communication and signaling : CCS · 2026Review
- Combinational Analysis of Metabolomic and O-GlcNAcylation Omics Reveals the HBP Metabolic Regulation of Chemoresistance via GFPT1/NR3C1 O-GlcNAcylation/GPX4 Axis.Research (Washington, D.C.) · 2025Article
- Glucocorticoid receptors orchestrate a convergence of host and cellular stress signals in triple negative breast cancer.The Journal of steroid biochemistry and molecular biology · 2024Review
- The Glucocorticoid Receptor: Isoforms, Functions, and Contribution to Glucocorticoid Sensitivity.Endocrine reviews · 2024Review
- Acetylation-induced proteasomal degradation of the activated glucocorticoid receptor limits hormonal signaling.iScience · 2024Article
- Emerging Epigenetic and Posttranslational Mechanisms Controlling Resistance to Glucocorticoids in Acute Lymphoblastic Leukemia.HemaSphere · 2023Review
- RNA binding by the glucocorticoid receptor attenuates dexamethasone-induced gene activation.Scientific reports · 2023Article
- Apoptotic, Anti-Inflammatory Activities and Interference with the Glucocorticoid Receptor Signaling of Fractions fromPlants (Basel, Switzerland) · 2022Article
- Oncogenic Activity of Glucocorticoid Receptor β Is Controlled by Ubiquitination-Dependent Interaction with USP49 in Glioblastoma Cells.Molecular cancer research : MCR · 2022Article
- Stress sensing within the breast tumor microenvironment: how glucocorticoid receptors live in the moment.Essays in biochemistry · 2021Review
- Review
- Glucocorticoid Resistance: Interference between the Glucocorticoid Receptor and the MAPK Signalling Pathways.International journal of molecular sciences · 2021Review
- Glucocorticoid Receptor: A Multifaceted Actor in Breast Cancer.International journal of molecular sciences · 2021Review
- Posttranslational Modifications of the Mineralocorticoid Receptor and Cardiovascular Aging.Frontiers in molecular biosciences · 2021Review
- Proteasome inhibition creates a chromatin landscape favorable to RNA Pol II processivity.The Journal of biological chemistry · 2020Article
- Multifaceted Control of GR Signaling and Its Impact on Hepatic Transcriptional Networks and Metabolism.Frontiers in endocrinology · 2020Review
- β-Arrestin-1 inhibits glucocorticoid receptor turnover and alters glucocorticoid signaling.The Journal of biological chemistry · 2019Article
- GR Dimerization and the Impact of GR Dimerization on GR Protein Stability and Half-Life.Frontiers in immunology · 2019Review
- Disease- and treatment-associated acquired glucocorticoid resistance.Endocrine connections · 2018Review
- Novel role for receptor dimerization in post-translational processing and turnover of the GRα.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Glucocorticoid receptors (GRs) are members of a highly conserved family of ligand dependent transcription factors which following hormone binding undergo homologous down-regulation reducing the levels of receptor protein. This decline in human GR (hGR) is due in part to a decrease in protein receptor stability that may limit cellular responsiveness to ligand. To examine the role of the proteasome protein degradation pathway in steroid-dependent hGR responsiveness, we utilized the proteasomal inhibitors MG-132, beta-lactone, and epoxomicin. HeLa cells and COS cells were treated with proteasome inhibitors in the presence of the GR agonist dexamethasone (Dex), or were pretreated with proteasomal inhibitor and then Dex. Dexamethasone induced glucocorticoid responsive reporter activity significantly over untreated controls, whereas cells treated with proteasomal inhibitors and Dex together showed 2-3-fold increase in activity. Protein sequence analysis of the hGR protein identified several candidate protein degradation motifs including a PEST element. Mutagenesis of this element at lysine 419 was done and mutant K419A hGR failed to undergo ligand dependent down-regulation. Mutant K419A hGR displayed 2-3-fold greater glucocorticoid responsive reporter activity in the presence of Dex than wild type hGR. These differences in transcriptional activity were not due to altered subcellular localization, since when the mutant K419A hGR was fused with the green fluorescent protein (GFP) it was found to move in and out of the nucleus similarly to wild type hGR. Together these results suggest that the proteasome and the identified PEST degradation motif limit steroid-dependent human glucocorticoid receptor signaling.
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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.