ArticleCell death & disease2014
The bromodomain protein BRD4 regulates the KEAP1/NRF2-dependent oxidative stress response.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 121 citations in OpenAlex.
- The cell with many faces: lung macrophage plasticity and function in response to environmental and pathogenic insults.Physiological reviews · 2026Review
- BRD2 upregulation as a pan-cancer adaptive resistance mechanism to BET inhibition.Cellular & molecular biology letters · 2026Article
- BRD4 modulates antimicrobial defense via non-canonical NRF2 activation in macrophages to confer protection against sepsis.PLoS pathogens · 2026Article
- BRD2 Upregulation as a Pan-Cancer Adaptive Resistance Mechanism to BET Inhibition.bioRxiv : the preprint server for biology · 2025Article
- Inhibition of bromodomain and extra-terminal (BET) proteins with JQ1 exacerbates acetaminophen-induced hepatotoxicity by altering detoxification pathways and oxidative stress responses.Chemico-biological interactions · 2025Article
- The HAT Inhibitor ISOX-DUAL Diminishes Ischemic Areas in a Mouse Model of Oxygen-Induced Retinopathy.Genes to cells : devoted to molecular & cellular mechanisms · 2025Article
- Inhibition of BRD4 activates the AKT-SIRT3 signaling pathway to suppress apoptosis and attenuate hyperoxia-induced lung injury.Frontiers in bioengineering and biotechnology · 2025Article
- The BRD4 Inhibitor I-BET-762 Reduces HO-1 Expression in Macrophages and the Pancreas of Mice.International journal of molecular sciences · 2024Article
- Genome-Wide CRISPR Screen Identifies KEAP1 Perturbation as a Vulnerability of ARID1A-Deficient Cells.Cancers · 2024Article
- A Novel BD2-Selective Inhibitor of BRDs Mitigates ROS Production and OA Pathogenesis.Antioxidants (Basel, Switzerland) · 2024Article
- BRD3 Regulates the Inflammatory and Stress Response in Rheumatoid Arthritis Synovial Fibroblasts.Biomedicines · 2023Article
- BET Protein Inhibitor JQ1 Ameliorates Experimental Peritoneal Damage by Inhibition of Inflammation and Oxidative Stress.Antioxidants (Basel, Switzerland) · 2023Article
- Review
- BET Protein Inhibitor JQ1 Modulates Mitochondrial Dysfunction and Oxidative Stress Induced by Chronic Kidney Disease.Antioxidants (Basel, Switzerland) · 2023Article
- Article
- Fucoxanthin inhibits cardiac fibroblast transdifferentiation by alleviating oxidative stress through downregulation of BRD4.PloS one · 2023Article
- EGFR-induced suppression of HPV E6/E7 is mediated by microRNA-9-5p silencing of BRD4 protein in HPV-positive head and neck squamous cell carcinoma.Cell death & disease · 2022Article
- Small Molecule BRD4 Inhibitors Apabetalone and JQ1 Rescues Endothelial Cells Dysfunction, Protects Monolayer Integrity and Reduces Midkine Expression.Molecules (Basel, Switzerland) · 2022Article
- Pretreatment of nucleus pulposus mesenchymal stem cells with appropriate concentration of HStem cell research & therapy · 2022Article
- Targeted BRD4 protein degradation by dBET1 ameliorates acute ischemic brain injury and improves functional outcomes associated with reduced neuroinflammation and oxidative stress and preservation of blood-brain barrier integrity.Journal of neuroinflammation · 2022Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The epigenetic sensor BRD4 (bromodomain protein 4) is a potent target for anti-cancer therapies. To study the transcriptional impact of BRD4 in cancer, we generated an expression signature of BRD4 knockdown cells and found oxidative stress response genes significantly enriched. We integrated the RNA-Seq results with DNA-binding sites of BRD4 generated by chromatin immunoprecipitations, correlated these with gene expressions from human prostate cancers and identified 21 top BRD4 candidate genes among which the oxidative stress pathway genes KEAP1, SESN3 and HDAC6 are represented. Knock down of BRD4 or treatment with the BRD4 inhibitor JQ1 resulted in decreased reactive oxygen species (ROS) production and increased cell viability under H2O2 exposure. Consistently, a deregulation of BRD4 diminished the KEAP1/NRF2 axis and led to a disturbed regulation of the inducible heme oxygenase 1 (HMOX1). Without exogenous stress induction, we also found BRD4 directly targeting the HMOX1 promoter over the SP1-binding sites. Our findings provide insight into the transcriptional regulatory network of BRD4 and highlight BRD4 as signal transducer of the cellular response to oxidative stress.
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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.