ArticleMolecular and cellular biology2005
Glucocorticoid receptor (GR)-associated SMRT binding to C/EBPbeta TAD and Nrf2 Neh4/5: role of SMRT recruited to GR in GSTA2 gene repression.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 141 citations in OpenAlex.
- Bromodomain and extraterminal proteins suppress NF-E2-related factor 2-mediated antioxidant gene expression.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Interplay between NRF2 post-translational modifications and protein-protein interactions: Perspectives from emerging structural and functional evidence.Archives of biochemistry and biophysics · 2026Review
- Beyond KEAP1: The Context-Specific NRF2 Partner Code in Disease and Therapy.Antioxidants (Basel, Switzerland) · 2026Review
- Nrf2: A Promising Therapeutic Target for Glucocorticoid-Resistant Chronic Rhinosinusitis.Clinical and experimental otorhinolaryngology · 2026Review
- The Glucocorticoid Receptor Inhibits NRF2-Mediated Expression of SLC7A11.Free radical biology & medicine · 2025Article
- NRF2 activation in cancer and overview of NRF2 small molecule inhibitors.Archives of pharmacal research · 2025Review
- Review
- Overview of Nrf2 as a target in ovary and ovarian dysfunctions focusing on its antioxidant properties.Journal of ovarian research · 2025Review
- Selenium Yeast AlleviatesAnimals : an open access journal from MDPI · 2025Article
- Novel putative causal mutations associated with fat traits in Nellore cattle uncovered by eQTLs located in open chromatin regions.Scientific reports · 2024Article
- Unique and overlapping roles of NRF2 and NRF1 in transcriptional regulation.Journal of clinical biochemistry and nutrition · 2024Article
- How to deal with frenemy NRF2: Targeting NRF2 for chemoprevention and cancer therapy.Journal of food and drug analysis · 2023Review
- Roles of Oxidative Stress and Nrf2 Signaling in Pathogenic and Non-Pathogenic Cells: A Possible General Mechanism of Resistance to Therapy.Antioxidants (Basel, Switzerland) · 2023Review
- Review
- Article
- Advances in Immunosuppressive Agents Based on Signal Pathway.Frontiers in pharmacology · 2022Review
- Targeting NLRP3 Inflammasome With Nrf2 Inducers in Central Nervous System Disorders.Frontiers in immunology · 2022Review
- Targeting NRF2 to treat cancer.Seminars in cancer biology · 2021Review
- Cooperation between NRF2-mediated transcription and MDIG-dependent epigenetic modifications in arsenic-induced carcinogenesis and cancer stem cells.Seminars in cancer biology · 2021Review
- Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The expression of the glutathione S-transferase gene (GST), whose induction accounts for cancer chemoprevention, is regulated by activation of CCAAT/enhancer binding protein beta (C/EBPbeta) and NF-E2-related factor 2 (Nrf2). The present study investigated the repressing effects of activating glucocorticoid receptor (GR) on C/EBPbeta- and Nrf2-mediated GSTA2 gene induction and the mechanism. Dexamethasone that activates GR inhibited constitutive and oltipraz- or tert-butylhydroquinone (t-BHQ)-inducible GSTA2 expression in H4IIE cells. Also, dexamethasone repressed GSTA2 promoter-luciferase gene activity. Dexamethasone-GR activation did not inhibit nuclear translocation of C/EBPbeta or Nrf2 nor their DNA binding activities induced by oltipraz or t-BHQ. Deletion of the glucocorticoid response element (GRE) in the GSTA2 promoter abolished dexamethasone inhibition of the gene induction. Immunoprecipitation-immunoblotting, chromatin immunoprecipitation, and GST pull-down assays revealed that silencing mediator for retinoid and thyroid hormone receptors (SMRT), a corepressor recruited to steroid-GR complex for histone deacetylation, bound to TAD domain of C/EBPbeta and Neh4/5 domain of Nrf2. The GSTA2 promoter-luciferase activities were decreased by SMRT but not by truncated SMRTs. The small interference RNA (siRNA) against SMRT abolished SMRT repression of the gene induction by C/EBPbeta or Nrf2. The plasmid transfection and siRNA experiments directly evidenced the functional role of SMRT in GSTA2 repression. In conclusion, dexamethasone antagonizes C/EBPbeta- and Nrf2-mediated GSTA2 gene induction via ligand-GR binding to the GRE, and steroid-mediated GSTA2 repression involves inactivation of C/EBPbeta and Nrf2 by SMRT recruited to steroid-GR complex.
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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.