ArticleMolecular cell2024
Phosphorylation by JNK switches BRD4 functions.
Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Cell Type-Specific Roles for BRD4 in Heart Failure.Current cardiology reports · 2026Review
- BRD4: From molecular understanding to therapeutics development.Molecular cell · 2026Review
- Protective effect of Caftaric Acid against hepatic cold ischemia/reperfusion injury in the liver.Biology direct · 2026Article
- From Yin-deficiency to therapy: molecular mechanisms and drug discovery in high-grade serous ovarian cancer.Journal of ovarian research · 2026Article
- Targeted inhibition of the CREB1-CtIP axis enhances the efficacy of abiraterone combined with radiotherapy in prostate cancer.Cell death & disease · 2026Article
- From chromosomal protein disorder to chromatin phase separation.Epigenetics & chromatin · 2026Review
- Direct Readout of Multivalent Chromatin Reader-Nucleosome Interactions by Nucleosome Mass Spectrometry.ACS central science · 2026Article
- Bromodomain-containing protein 4 in inflammatory diseases: molecular mechanisms and therapeutic potential.Journal of inflammation (London, England) · 2026Review
- BRD2 bridges TFIID and MOF-H4K16ac-containing nucleosomes to promote transcriptional initiation.Molecular cell · 2026Article
- Preclinical evaluation of JQ1 in esophageal squamous cell carcinoma: growth and migration suppression with BRD4-associated DNA damage and apoptotic signaling.Frontiers in pharmacology · 2026Article
- BRD4 inhibition suppresses histone H4 UFMylation to increase ferroptosis sensitivity through TXNIP.Cell death & disease · 2025Article
- CD24 is a promising immunotherapeutic target for enhancing efficacy of third-generation EGFR-TKIs on EGFR-mutated lung cancer.Cancer communications (London, England) · 2025Article
- BRD4 regulates Aurora B kinase activity.bioRxiv : the preprint server for biology · 2025Article
- Article
- Quantitative phosphoproteomics reveals that nestin is a downstream target of dual leucine zipper kinase during retinoic acid-induced neuronal differentiation of Neuro-2a cells.BMC molecular and cell biology · 2025Article
- A novel carboxamide bromodomain inhibitor attenuates osteoarthritis via epigenetic repression of NF-κB and MAPK signaling.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Bromodomain 4 (BRD4), a key regulator with pleiotropic functions, plays crucial roles in cancers and cellular stress responses. It exhibits dual functionality: chromatin-bound BRD4 regulates remodeling through its histone acetyltransferase (HAT) activity, while promoter-associated BRD4 regulates transcription through its kinase activity. Notably, chromatin-bound BRD4 lacks kinase activity, and RNA polymerase II (RNA Pol II)-bound BRD4 exhibits no HAT activity. This study unveils one mechanism underlying BRD4's functional switch. In response to diverse stimuli, c-Jun N-terminal kinase (JNK)-mediated phosphorylation of human BRD4 at Thr1186 and Thr1212 triggers its transient release from chromatin, disrupting its HAT activity and potentiating its kinase activity. Released BRD4 directly interacts with and phosphorylates RNA Pol II, PTEFb, and c-Myc, thereby promoting transcription of target genes involved in immune and inflammatory responses. JNK-mediated BRD4 functional switching induces CD8 expression in thymocytes and epithelial-to-mesenchymal transition (EMT) in prostate cancer cells. These findings elucidate the mechanism by which BRD4 transitions from a chromatin regulator to a transcriptional activator.
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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.