ArticleCancers2020
Bromodomain-Containing Protein BRD4 Is Hyperphosphorylated in Mitosis.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- BRD4: From molecular understanding to therapeutics development.Molecular cell · 2026Review
- Phosphoproteome Remodeling upon CDK1 Inhibition Restricts HSV-1 IE Gene Transcription and Replication.Cells · 2026Article
- ALG3 as a PanCancer Oncogene: Bioinformatics Analysis and Identification of Small-Molecule Inhibitors.Anti-cancer agents in medicinal chemistry · 2026Article
- CENP-F promotes HCC cell proliferation mediated by super enhancer reader BRD4.Discover oncology · 2025Article
- Gαq-Stimulated Gene Expression Is Insensitive to Bromo Extra Terminal Domain Inhibitors in HEK 293 Cells.International journal of molecular sciences · 2025Article
- A Minireview on BET Inhibitors: Beyond Bromodomain Targeting.Biomedicines · 2025Review
- Phosphorylation by JNK switches BRD4 functions.Molecular cell · 2024Article
- Elevating PLK1 overcomes BETi resistance in prostate cancer via triggering BRD4 phosphorylation-dependent degradation in mitosis.Cell reports · 2024Article
- Article
- Prediction of the interaction betweenHeliyon · 2023Article
- Proteomics of Plasma and Plasma-Treated Podocytes: Application to Focal and Segmental Glomerulosclerosis.International journal of molecular sciences · 2023Article
- BMS-265246, a Cyclin-Dependent Kinase Inhibitor, Inhibits the Infection of Herpes Simplex Virus Type 1.Viruses · 2023Article
- Integration of Chemoinformatics and Multi-Omics Analysis Defines ECT2 as a Potential Target for Cancer Drug Therapy.Biology · 2023Article
- BRD4 promotes resection and homology-directed repair of DNA double-strand breaks.Nature communications · 2022Article
- Post-Translational Modifications of BRD4: Therapeutic Targets for Tumor.Frontiers in oncology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The epigenetic reader BRD4 binds acetylated histones and plays a central role in controlling cellular gene transcription and proliferation. Dysregulation of BRD4's activity has been implicated in the pathogenesis of a wide variety of cancers. While blocking BRD4 interaction with acetylated histones using BET inhibitors (BETis) has been tested in clinical trials, many cancers have acquired BETi resistance. However, the underlying mechanisms are poorly understood and BETi resistance remains a pressing clinical problem. We previously showed that BRD4 phosphorylation supports stronger chromatin binding and target oncogene expression. In this study, we discovered that BRD4 is hyperphosphorylated by CDK1 during mitosis and determined the major CDK1 phosphorylation sites in BRD4. Using CRISPR/Cas9 gene editing, we replaced endogenous BRD4 with a non-phosphorylatable mutant and demonstrated that CDK1-mediated BRD4 phosphorylation contributes to BETi resistance. CDK1 over-activation frequently observed in cancers has the potential to cause aberrant BRD4 hyperphosphorylation persisting outside of mitosis to strengthen its target gene binding and confer BETi resistance. We found that dual CDK1 and BET inhibition generates a synergistic effect in killing BETi-resistant cancer cells. Our study therefore suggests that CDK1 inhibition can be employed to overcome tumor BETi resistance and improve treatments for BRD4-associated cancers.
Indexed as
Identifiers
What OpenQuestion holds
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.