ArticleProceedings of the National Academy of Sciences of the United States of America2009
A tumor suppressive coactivator complex of p53 containing ASC-2 and histone H3-lysine-4 methyltransferase MLL3 or its paralogue MLL4.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers, 1 of them a synthesis that pooled it.
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Who cites it
146 citing papers in PubMed, 1 synthesis or guideline pooled it, 216 citations in OpenAlex.
- Genetic alterations of histone lysine methyltransferases and their significance in breast cancer.Oncotarget · 2015Pooled it
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- The adenovirus oncoprotein E1B-55K reshapes epigenetic histone modifications in primary human cells.mBio · 2026Article
- Genomic Profiling of Laryngeal Squamous Cell Carcinoma Reveals Novel Biomarkers for Precision Medicine.Journal of personalized medicine · 2025Article
- KMT2C inactivation leads to PTEN downregulation and tolerance to DNA damage during cell cycle progression.NPJ precision oncology · 2025Article
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- p53 reveals principles of chromatin remodeling and enhancer activation.Nucleic acids research · 2025Article
- The epigenetic basis of hepatocellular carcinoma - mechanisms and potential directions for biomarkers and therapeutics.British journal of cancer · 2025Review
- PTEN loss drives p53 LOH and immune evasion in a novel urothelial organoid model harboring p53 missense mutations.Oncogene · 2025Article
- The MLL3/GRHL2 complex regulates malignant transformation and anti-tumor immunity in squamous cancer.The Journal of experimental medicine · 2025Article
- Role of histone-lysine N-methyltransferase 2D (KMT2D) in MEK-ERK signaling-mediated epigenetic regulation: a phosphoproteomics perspective.Frontiers in bioinformatics · 2025Article
- Next-Generation Integrated Sequencing Identifies Poor Prognostic Factors in Patients with MYD88-Mutated Chronic Lymphocytic Leukemia in Taiwan.Pathobiology : journal of immunopathology, molecular and cellular biology · 2025Article
- Loss of Kmt2c or Kmt2d primes urothelium for tumorigenesis and redistributes KMT2A-menin to bivalent promoters.Nature genetics · 2025Article
- Mapping in silico genetic networks of the KMT2D tumour suppressor gene to uncover novel functional associations and cancer cell vulnerabilities.Genome medicine · 2024Article
- Transcriptome and microbiome-immune changes across preinvasive and invasive anal cancer lesions.JCI insight · 2024Article
- SomaticJournal of thoracic disease · 2024Article
- Unveiling the Molecular Landscape of Pancreatic Ductal Adenocarcinoma: Insights into the Role of the COMPASS-like Complex.International journal of molecular sciences · 2024Review
- Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2024Review
86 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
ASC-2, a multifunctional coactivator, forms a steady-state complex, named ASCOM (for ASC-2 COMplex), that contains the histone H3-lysine-4 (H3K4)-methyltransferase MLL3 or its paralogue MLL4. Somewhat surprisingly, given prior indications of redundancy between MLL3 and MLL4, targeted inactivation of the MLL3 H3K4-methylation activity in mice is found to result in ureter epithelial tumors. Interestingly, this phenotype is exacerbated in a p53(+/-) background and the tumorigenic cells are heavily immunostained for gammaH2AX, indicating a contribution of MLL3 to the DNA damage response pathway through p53. Consistent with the in vivo observations, and the demonstration of a direct interaction between p53 and ASCOM, cell-based assays have revealed that ASCOM, through ASC-2 and MLL3/4, acts as a p53 coactivator and is required for H3K4-trimethyation and expression of endogenous p53-target genes in response to the DNA damaging agent doxorubicin. In support of redundant functions for MLL3 and MLL4 for some events, siRNA-mediated down-regulation of both MLL3 and MLL4 is required to suppress doxorubicin-inducible expression of several p53-target genes. Importantly, this study identifies a specific H3K4 methytransferase complex, ASCOM, as a physiologically relevant coactivator for p53 and implicates ASCOM in the p53 tumor suppression pathway in vivo.
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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.