ArticleThe Journal of biological chemistry2011
Perturbation of BRD4 protein function by BRD4-NUT protein abrogates cellular differentiation in NUT midline carcinoma.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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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.
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Who cites it
36 citing papers in PubMed, 60 citations in OpenAlex.
- NSD3 stabilizes nuclear compartmentalization and promotes megabase-scale chromatin interactions.bioRxiv : the preprint server for biology · 2026Article
- Targeted inhibition of BET proteins in HPV16-positive head and neck squamous cell carcinoma reveals heterogeneous transcriptional responses.Frontiers in oncology · 2024Article
- Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.Signal transduction and targeted therapy · 2023Review
- Structural mechanism of BRD4-NUT and p300 bipartite interaction in propagating aberrant gene transcription in chromatin in NUT carcinoma.Nature communications · 2023Article
- Structural insights into p300 regulation and acetylation-dependent genome organisation.Nature communications · 2022Article
- Epigenetics in Pancreatic Ductal Adenocarcinoma: Impact on Biology and Utilization in Diagnostics and Treatment.Cancers · 2022Review
- Review
- Leveraging epigenetics to enhance the efficacy of immunotherapy.Clinical epigenetics · 2021Review
- Immunotherapy and Targeting the Tumor Microenvironment: Current Place and New Insights in Primary Pulmonary NUT Carcinoma.Frontiers in oncology · 2021Review
- Article
- Chromatin Hyperacetylation Impacts Chromosome Folding by Forming a Nuclear Subcompartment.Molecular cell · 2020Article
- Fusion transcripts: Unexploited vulnerabilities in cancer?Wiley interdisciplinary reviews. RNA · 2020Review
- Genomic variation as a marker of response to neoadjuvant therapy in locally advanced rectal cancer.Molecular & cellular oncology · 2020Article
- "Z4" Complex Member Fusions in NUT Carcinoma: Implications for a Novel Oncogenic Mechanism.Molecular cancer research : MCR · 2018Article
- Targeting Epigenetics in Cancer.Annual review of pharmacology and toxicology · 2018Review
- Molecular-genetic profiling and high-throughputOncotarget · 2017Article
- Systematic Kinase Inhibitor Profiling Identifies CDK9 as a Synthetic Lethal Target in NUT Midline Carcinoma.Cell reports · 2017Article
- Targeting Cancer Cells with BET Bromodomain Inhibitors.Cold Spring Harbor perspectives in medicine · 2017Review
- Uncovering BRD4 hyperphosphorylation associated with cellular transformation in NUT midline carcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- The Bromodomain and Extra-Terminal Domain (BET) Family: Functional Anatomy of BET Paralogous Proteins.International journal of molecular sciences · 2016Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
NUT midline carcinoma (NMC) belongs to a class of highly lethal and poorly differentiated epithelial cancers arising mainly in human midline organs. NMC is caused by the chromosome translocation-mediated fusion of the NUT (nuclear protein in testis) gene on chromosome 15 to a few other genes, most frequently the BRD4 gene on chromosome 19. The mechanism by which the BRD4-NUT fusion product blocks NMC cellular differentiation and contributes to oncogenesis remains elusive. In this study, we show that BRD4-NUT and BRD4 colocalize in discrete nuclear foci that are hyperacetylated but transcriptionally inactive. BRD4-NUT recruits histone acetyltransferases to induce histone hyperacetylation in these chromatin foci, which provide docking sites for accumulation of additional BRD4 and associated P-TEFB (positive transcription elongation factor b) complexes in the transcriptionally inactive BRD4-NUT foci. These molecular events lead to repression of a BRD4·P-TEFB downstream target gene c-fos, a component of activator protein 1 (AP-1), that directly regulates epithelial differentiation. Knockdown of BRD4-NUT in NMC cells disperses the transcriptionally inactive chromatin foci and releases the transcriptional activators to stimulate c-fos expression, leading to restoration of cellular differentiation. Our study provides a novel mechanism by which the BRD4-NUT oncogene perturbs BRD4 functions to block cellular differentiation and to contribute to the oncogenic progression in the highly aggressive NMC.
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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.