ArticleCancer discovery2015
Lysine demethylase KDM4A associates with translation machinery and regulates protein synthesis.
Article in Cancer discovery, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 72 citations in OpenAlex.
- Lysine demethylase 4A: from chromatin to centrosomes.The FEBS journal · 2026Article
- Lysine demethylase 4A is a centrosome-associated protein required for centrosome integrity and genomic stability.The FEBS journal · 2026Article
- Epigenetic, ribosomal, and immune dysregulation in paediatric acute-onset neuropsychiatric syndrome.Molecular psychiatry · 2025Article
- KDM4A serves as an α-tubulin demethylase regulating microtubule polymerization and cell mitosis.Science advances · 2025Article
- Review
- Analogue-Sensitive Inhibition of Histone Demethylases Uncovers Member-Specific Function in Ribosomal Protein Synthesis.Journal of the American Chemical Society · 2025Article
- Versatile JMJD proteins: juggling histones and much more.Trends in biochemical sciences · 2024Review
- Epigenetic modulators provide a path to understanding disease and therapeutic opportunity.Genes & development · 2024Review
- Oncogenic Cells of Renal Embryonic Lineage Sensitive to the Small-Molecule Inhibitor QC6352 Display Depletion of KDM4 Levels and Disruption of Ribosome Biogenesis.Molecular cancer therapeutics · 2024Article
- Histone lysine demethylase 4 family proteins maintain the transcriptional program and adrenergic cellular state of MYCN-amplified neuroblastoma.Cell reports. Medicine · 2024Article
- SET7/9-mediated methylation affects oncogenic functions of histone demethylase JMJD2A.JCI insight · 2023Article
- Activity Guided Azide-methyllysine Photo-trapping for Substrate Profiling of Lysine Demethylases.Journal of the American Chemical Society · 2023Article
- A Novel Class of Ribosome Modulating Agents Exploits Cancer Ribosome Heterogeneity to Selectively Target the CMS2 Subtype of Colorectal Cancer.Cancer research communications · 2023Article
- KDM4 Demethylases: Structure, Function, and Inhibitors.Advances in experimental medicine and biology · 2023Article
- The histone methyltransferase SETD2 negatively regulates cell size.Journal of cell science · 2022Article
- IDH-mutated gliomas promote epileptogenesis through d-2-hydroxyglutarate-dependent mTOR hyperactivation.Neuro-oncology · 2022Article
- The Interaction of SWI/SNF with the Ribosome Regulates Translation and Confers Sensitivity to Translation Pathway Inhibitors in Cancers with Complex Perturbations.Cancer research · 2022Article
- Recent Advances with KDM4 Inhibitors and Potential Applications.Journal of medicinal chemistry · 2022Review
- Epigenetics of Cutaneous T-Cell Lymphomas.International journal of molecular sciences · 2022Review
- Multi-omics analyses of the ulcerative colitis gut microbiome link Bacteroides vulgatus proteases with disease severity.Nature microbiology · 2022Article
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8 authors at 2 institutions in 2 countries.
Funding
Abstract
unlabelledChromatin-modifying enzymes are predominantly nuclear; however, these factors are also localized to the cytoplasm, and very little is known about their role in this compartment. In this report, we reveal a non-chromatin-linked role for the lysine-specific demethylase KDM4A. We demonstrate that KDM4A interacts with the translation initiation complex and affects the distribution of translation initiation factors within polysome fractions. Furthermore, KDM4A depletion reduced protein synthesis and enhanced the protein synthesis suppression observed with mTOR inhibitors, which paralleled an increased sensitivity to these drugs. Finally, we demonstrate that JIB-04, a JmjC demethylase inhibitor, suppresses translation initiation and enhances mTOR inhibitor sensitivity. These data highlight an unexpected cytoplasmic role for KDM4A in regulating protein synthesis and suggest novel potential therapeutic applications for this class of enzyme. SIGNIFICANCE: This report documents an unexpected cytoplasmic role for the lysine demethylase KDM4A. We demonstrate that KDM4A interacts with the translation initiation machinery, regulates protein synthesis and, upon coinhibition with mTOR inhibitors, enhances the translation suppression and cell sensitivity to these therapeutics.
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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.