ArticlePloS one2015
The selective activation of p53 target genes regulated by SMYD2 in BIX-01294 induced autophagy-related cell death.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 37 citations in OpenAlex.
- The Trajectory of Epigenetic Chromatin Remodeling in Cardiometabolic Disease and its Therapeutic Implications.Journal of cardiovascular translational research · 2026Review
- The Role of Histone Methylation in Heart Failure: Epigenetic Mechanisms and Therapeutic Perspectives.Drug design, development and therapy · 2026Review
- Cinnamaldehyde induces autophagy-mediated cell death through ER stress and epigenetic modification in gastric cancer cells.Acta pharmacologica Sinica · 2022Article
- Epigenetic Dysregulation Induces Translocation of Histone H3 into Cytoplasm.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Structure Based Design of Bicyclic Peptide Inhibitors of RbAp48.Angewandte Chemie (International ed. in English) · 2021Article
- Histone Methylation Related Therapeutic Challenge in Cardiovascular Diseases.Frontiers in cardiovascular medicine · 2021Review
- USP22 exerts tumor-suppressive functions in colorectal cancer by decreasing mTOR activity.Cell death and differentiation · 2020Article
- EHMT2 Inhibition Induces Cell Death in Human Non-Small Cell Lung Cancer by Altering the Cholesterol Biosynthesis Pathway.International journal of molecular sciences · 2020Article
- Epigenetic Control of Autophagy in Cancer Cells: A Key Process for Cancer-Related Phenotypes.Cells · 2019Review
- Article
- Protein methylation functions as the posttranslational modification switch to regulate autophagy.Cellular and molecular life sciences : CMLS · 2019Review
- Histone methyltransferase SMYD2: ubiquitous regulator of disease.Clinical epigenetics · 2019Review
- Histone demethylase KDM3A is required for enhancer activation of hippo target genes in colorectal cancer.Nucleic acids research · 2019Article
- Histone methyl-transferases and demethylases in the autophagy regulatory network: the emerging role of KDM1A/LSD1 demethylase.Autophagy · 2019Review
- BIX-01294 sensitizes renal cancer Caki cells to TRAIL-induced apoptosis through downregulation of survivin expression and upregulation of DR5 expression.Cell death discovery · 2018Article
- Accumulation of low-dose BIX01294 promotes metastatic potential of U251 glioblastoma cells.Oncology letters · 2017Article
- BIX01294, an inhibitor of histone methyltransferase, induces autophagy-dependent differentiation of glioma stem-like cells.Scientific reports · 2016Article
- Discovery and Characterization of a Highly Potent and Selective Aminopyrazoline-Based in Vivo Probe (BAY-598) for the Protein Lysine Methyltransferase SMYD2.Journal of medicinal chemistry · 2016Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transcription regulation emerged to be one of the key mechanisms in regulating autophagy. Inhibitors of H3K9 methylation activates the expression of LC3B, as well as other autophagy-related genes, and promotes autophagy process. However, the detailed mechanisms of autophagy regulated by nuclear factors remain elusive. In this study, we performed a drug screen of SMYD2-/- cells and discovered that SMYD2 deficiency enhanced the cell death induced by BIX01294, an inhibitor of histone H3K9 methylation. BIX-01294 induces accumulation of LC3 II and autophagy-related cell death, but not caspase-dependent apoptosis. We profiled the global gene expression pattern after treatment with BIX-01294, in comparison with rapamycin. BIX-01294 selectively activates the downstream genes of p53 signaling, such as p21 and DOR, but not PUMA, a typical p53 target gene inducing apoptosis. BIX-01294 also induces other autophagy-related genes, such as ATG4A and ATG9A. SMYD2 is a methyltransferase for p53 and regulates its transcription activity. Its deficiency enhances the BIX-01294-induced autophagy-related cell death through transcriptionally promoting the expression of p53 target genes. Taken together, our data suggest BIX-01294 induces autophagy-related cell death and selectively activates p53 target genes, which is repressed by SMYD2 methyltransferase.
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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.