ArticleGenome medicine2020
ASXL3 bridges BRD4 to BAP1 complex and governs enhancer activity in small cell lung cancer.
Article in Genome medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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
36 citing papers in PubMed, 60 citations in OpenAlex.
- Polycomb repressive-deubiquitinase complex safeguards oocyte epigenome and female fertility by restraining Polycomb activity.Nature communications · 2026Article
- Subtype-specific dependencies and therapeutic opportunities in small cell lung cancer.Science advances · 2026Review
- Recruitment of BRD4 to the ASXL1 genomic targets depends on the extra-terminal domain of BRD4.Nature communications · 2026Article
- SPAP: Soluble Human Plasma Proteoform Analysis via Acetonitrile Precipitation and Top-Down Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2026Article
- Pathological role of deubiquitinating enzymes in lung cancer: recent insights and advances.American journal of cancer research · 2026Review
- UFMylation maintains tumor suppressor pVHL stability by activating the deubiquitinase BAP1.Science advances · 2025Article
- An epigenetic pathway regulates MHC-II expression and function in B cell lymphoma models.The Journal of clinical investigation · 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
- Integrative analysis of ASXL family genes reveals ASXL2 as an immunoregulatory molecule in head and neck squamous cell carcinoma.Scientific reports · 2024Article
- Identification and validation of a novel prognostic signature and key genes related to development of anaplastic thyroid carcinoma.Discover oncology · 2024Article
- Sex-specific survival gene mutations are discovered as clinical predictors of clear cell renal cell carcinoma.Scientific reports · 2024Article
- Additional Sex Combs-like Family Associated with Epigenetic Regulation.International journal of molecular sciences · 2024Review
- Peptide Inhibitor Targeting the Extraterminal Domain in BRD4 Potently Suppresses Breast Cancer BothJournal of medicinal chemistry · 2024Article
- A SWI/SNF-dependent transcriptional regulation mediated by POU2AF2/C11orf53 at enhancer.Nature communications · 2024Article
- Potential roles of UCH family deubiquitinases in tumorigenesis and chemical inhibitors developed against them.American journal of cancer research · 2024Review
- BET in hematologic tumors: Immunity, pathogenesis, clinical trials and drug combinations.Genes & diseases · 2023Review
- Iron drives anabolic metabolism through active histone demethylation and mTORC1.Nature cell biology · 2023Article
- PR-DUB safeguards Polycomb repression through H2AK119ub1 restriction.Cell proliferation · 2023Article
- Cardio-oncology: Shared Genetic, Metabolic, and Pharmacologic Mechanism.Current cardiology reports · 2023Review
- Therapeutic targeting of metabolic vulnerabilities in cancers with MLL3/4-COMPASS epigenetic regulator mutations.The Journal of clinical investigation · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundSmall cell lung cancer (SCLC) is a more aggressive subtype of lung cancer that often results in rapid tumor growth, early metastasis, and acquired therapeutic resistance. Consequently, such phenotypical characteristics of SCLC set limitations on viable procedural options, making it difficult to develop both screenings and effective treatments. In this study, we examine a novel mechanistic insight in SCLC cells that could potentially provide a more sensitive therapeutic alternative for SCLC patients.
methodsBiochemistry studies, including size exclusion chromatography, mass spectrometry, and western blot analysis, were conducted to determine the protein-protein interaction between additional sex combs-like protein 3 (ASXL3) and bromodomain-containing protein 4 (BRD4). Genomic studies, including chromatin immunoprecipitation sequencing (ChIP-seq), RNA sequencing, and genome-wide analysis, were performed in both human and mouse SCLC cells to determine the dynamic relationship between BRD4/ASXL3/BAP1 epigenetic axis in chromatin binding and its effects on transcriptional activity.
resultsWe report a critical link between BAP1 complex and BRD4, which is bridged by the physical interaction between ASXL3 and BRD4 in an SCLC subtype (SCLC-A), which expresses a high level of ASCL1. We further showed that ASXL3 functions as an adaptor protein, which directly interacts with BRD4's extra-terminal (ET) domain via a novel BRD4 binding motif (BBM), and maintains chromatin occupancy of BRD4 to active enhancers. Genetic depletion of ASXL3 results in a genome-wide reduction of histone H3K27Ac levels and BRD4-dependent gene expression in SCLC. Pharmacologically induced inhibition with BET-specific chemical degrader (dBET6) selectively inhibits cell proliferation of a subtype of SCLC that is characterized with high expression of ASXL3.
conclusionsCollectively, this study provides a mechanistic insight into the oncogenic function of BRD4/ASXL3/BAP1 epigenetic axis at active chromatin enhancers in SCLC-A subtype, as well as a potential new therapeutic option that could become more effective in treating SCLC patients with a biomarker of ASXL3-highly expressed SCLC cells.
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.