ArticleCell death & disease2013
Runt-related transcription factor 2 (RUNX2) inhibits p53-dependent apoptosis through the collaboration with HDAC6 in response to DNA damage.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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59 citing papers in PubMed, 89 citations in OpenAlex.
- Loss of MEG3 promotes migration and invasion of nickel-transformed cells, partially via upregulation of RUNX2.Toxicology and applied pharmacology · 2026Article
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- Paediatric therapeutic development workshop on osteosarcoma.British journal of cancer · 2026Review
- Molecular Crosstalk Between RUNX2 and HIF-1α in Osteosarcoma: Implications for Angiogenesis, Metastasis, and Therapy Resistance.International journal of molecular sciences · 2025Review
- The Role of HDAC6 in Glioblastoma Multiforme: A New Avenue to Therapeutic Interventions?Biomedicines · 2024Review
- Exploring the clinical potential of circulating LncRNAs in breast cancer: insights into primary signaling pathways and therapeutic interventions.Functional & integrative genomics · 2024Review
- RUNX transcription factors: biological functions and implications in cancer.Clinical and experimental medicine · 2024Review
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- RUNX2 Reverses p53-Induced Chemotherapy Resistance in Gastric Cancer.Pharmacogenomics and personalized medicine · 2023Article
- Identification of the Transcriptional Regulatory Role of RUNX2 by Network Analysis in Lung Cancer Cells.Biomedicines · 2022Article
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- HDAC6: A unique HDAC family member as a cancer target.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- YBX1 Promotes the Inclusion of RUNX2 Alternative Exon 5 in Dental Pulp Stem Cells.International journal of stem cells · 2022Article
- Regulatory Role of the RUNX2 Transcription Factor in Lung Cancer Apoptosis.International journal of cell biology · 2022Article
- Two Novel C-Terminus RUNX2 Mutations in Two Cleidocranial Dysplasia (CCD) Patients Impairing p53 Expression.International journal of molecular sciences · 2021Article
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Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Runt-related transcription factor 2 (RUNX2) is the best known as an essential protein for osteoblast differentiation. In this study, we have found for the first time that RUNX2 acts as a negative regulator for p53 in response to DNA damage. On DNA damage mediated by adriamycin (ADR) exposure, p53 as well as RUNX2 was induced at protein and mRNA level in human osteosarcoma-derived U2OS cells in association with a significant upregulation of various p53-target genes. Indirect immunostaining and co-immunoprecipitation experiments demonstrated that RUNX2 colocalizes with p53 in cell nucleus and forms a complex with p53 following ADR treatment. Chromatin immunoprecipitation assays revealed that RUNX2/p53 complex is efficiently recruited onto p53-target promoters in response to ADR, suggesting that RUNX2 might be involved in the regulation of transcriptional activation mediated by p53. Indeed, forced expression of RUNX2 resulted in a remarkable downregulation of p53-target genes. Consistent with these observations, knockdown of RUNX2 enhanced ADR-mediated apoptosis and also elevated p53-target gene expression in response to ADR. On the other hand, depletion of RUNX2 in p53-deficient human lung carcinoma-derived H1299 cells had an undetectable effect on p53-target gene expression regardless of ADR treatment, indicating that RUNX2-mediated downregulation of p53-target genes is dependent on p53. Furthermore, RUNX2/p53 complex included histone deacetylase 6 (HDAC6) and HDAC6 was also recruited onto p53-target promoters following ADR exposure. Of note, HDAC6-specific chemical inhibitor tubacin treatment enhanced ADR-mediated upregulation of p53-target gene expression, indicating that deacetylase activity of HDAC6 is required for RUNX2-mediated downregulation of p53-target gene. Taken together, our present findings strongly suggest that RUNX2 inhibits DNA damage-induced transcriptional as well as pro-apoptotic activity of p53 through the functional collaboration with HDAC6 and therefore might be an attractive therapeutic target for cancer treatment.
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