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Updated: May 26, 2026
Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay
Published on: June 9, 2017
DNA damage-induced RORα is crucial for p53 stabilization and increased apoptosis
Hyunkyung Kim1, Ji Min Lee, Gina Lee
1Department of Biological Sciences, Creative Research Initiative Center for Chromatin Dynamics, Seoul National University, Seoul 151-742, South Korea.
Abstract:
A critical component of the DNA damage response is the p53 tumor suppressor, and aberrant p53 function leads to uncontrolled cell proliferation and malignancy. Several molecules have been shown to regulate p53 stability; however, genome-wide systemic approaches for determining the affected, specific downstream target genes have not been extensively studied. Here, we first identified an orphan nuclear receptor, RORα, as a direct target gene of p53, which contains functional p53 response elements. The functional consequences of DNA damage-induced RORα are to stabilize p53 and activate p53 transcription in a HAUSP/Usp7-dependent manner. Interestingly, microarray analysis revealed that RORα-mediated p53 stabilization leads to the activation of a subset of p53 target genes that are specifically involved in apoptosis. We further confirmed that RORα enhances p53-dependent, in vivo apoptotic function in the Drosophila model system. Together, we determined that RORα is a p53 regulator that exerts its role in increased apoptosis via p53.
Insights
The tumor suppressor p53 is crucial for DNA damage response. This study identifies RORα as a p53 target gene that enhances p53 stability and promotes apoptosis, revealing a new regulatory pathway in cancer suppression.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- The p53 tumor suppressor is a critical regulator of the DNA damage response.
- Dysfunctional p53 is linked to uncontrolled cell proliferation and cancer.
- Systematic identification of p53 downstream targets is limited.
Purpose of the Study:
- To identify novel downstream target genes of p53.
- To investigate the role of RORα in p53 regulation and function.
- To elucidate the impact of RORα on p53-mediated apoptosis.
Main Methods:
- Identification of RORα as a direct p53 target gene using p53 response elements.
- Assessment of RORα's effect on p53 stabilization and transcription.
- Microarray analysis to identify RORα-regulated p53 target genes.
- In vivo apoptosis assays in a Drosophila model.
Main Results:
- RORα was identified as a direct p53 target gene.
- DNA damage-induced RORα stabilizes p53 and activates its transcription via HAUSP/Usp7.
- RORα enhances the activation of a subset of p53 target genes involved in apoptosis.
- RORα promotes p53-dependent apoptosis in vivo.
Conclusions:
- RORα acts as a novel regulator of p53.
- RORα enhances p53 stability and function, leading to increased apoptosis.
- This RORα-p53 pathway represents a potential therapeutic target for cancer treatment.
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