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Updated: May 12, 2026
09:16
Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
Published on: September 1, 2019
Runt-related transcription factor 2 (RUNX2) inhibits p53-dependent apoptosis through the collaboration with HDAC6 in
1Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute, Chiba, Japan. tozaki@chiba-cc.jp
Cell Death & Disease
|April 27, 2013
Summary
Runt-related transcription factor 2 (RUNX2) suppresses p53
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Runt-related transcription factor 2 (RUNX2) is primarily known for its role in osteoblast differentiation.
- The function of RUNX2 in DNA damage response pathways, particularly its interaction with p53, is not well understood.
Purpose of the Study:
- To investigate the novel role of RUNX2 as a regulator of p53 activity in response to DNA damage.
- To elucidate the molecular mechanisms underlying RUNX2's interaction with p53 and its impact on p53 target gene expression.
Main Methods:
- Utilized human osteosarcoma (U2OS) and lung carcinoma (H1299) cell lines.
- Employed adriamycin (ADR) to induce DNA damage.
- Performed indirect immunostaining, co-immunoprecipitation, chromatin immunoprecipitation (ChIP) assays, gene expression analysis (mRNA and protein levels), and knockdown/overexpression studies.
- Investigated the role of histone deacetylase 6 (HDAC6) and its inhibitor tubacin.
Main Results:
- RUNX2 and p53 protein and mRNA levels were induced upon ADR treatment in U2OS cells.
- RUNX2 formed a complex with p53 in the nucleus and was recruited to p53 target promoters.
- Forced expression of RUNX2 downregulated p53 target genes, while RUNX2 knockdown enhanced apoptosis and p53 target gene expression.
- RUNX2's effect on p53 target genes was p53-dependent.
- The RUNX2/p53 complex recruited HDAC6, and HDAC6's deacetylase activity was necessary for RUNX2-mediated downregulation of p53 target genes.
Conclusions:
- RUNX2 acts as a negative regulator of p53 in response to DNA damage.
- RUNX2 inhibits the transcriptional and pro-apoptotic activity of p53 through collaboration with HDAC6.
- This RUNX2-HDAC6-p53 axis presents a potential therapeutic target for cancer treatment.
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