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Updated: Jun 17, 2026
Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
Published on: September 28, 2012
Foxp3 expression in p53-dependent DNA damage responses
Da-Jung Jung1, Dong-Hoon Jin, Seung-Woo Hong
1Department of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine, Seoul 110-744, USA.
Abstract:
The forkhead transcription factor, Foxp3, is thought to act as a master regulator that controls (suppresses) expression of the breast cancer oncogenes, SKP2 and HER-2/ErbB2. However, the mechanisms that regulate Foxp3 expression and thereby modulate tumor development remain largely unexplored. Here, we demonstrate that Foxp3 up-regulation requires p53 function, showing that Foxp3 expression is directly regulated by p53 upon DNA damage responses in human breast and colon carcinoma cells. Treatment with the genotoxic agents, doxorubicin or etoposide, induced Foxp3 expression in p53-positive carcinoma cells, but not in cells lacking p53 function. Furthermore, knock down of endogenous wild-type p53 using RNA interference abrogated Foxp3 induction by genotoxic agents, and exogenous expression of p53 in cells lacking p53 restored the responsiveness of Foxp3 to DNA-damaging stresses. In addition, Foxp3 knock down blunted the p53-mediated growth inhibitory response to DNA-damaging agents. These results suggest that induction of Foxp3 in the context of tumor suppression is regulated in a p53-dependent manner and implicate Foxp3 as a key determinant of cell fate in p53-dependent DNA damage responses.
Insights
The tumor suppressor protein p53 directly regulates the transcription factor Foxp3, particularly after DNA damage. This p53-Foxp3 interaction is crucial for controlling cell growth and tumor suppression in cancer cells.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- The transcription factor Foxp3 is implicated in suppressing breast cancer oncogenes SKP2 and HER-2/ErbB2.
- Mechanisms governing Foxp3 expression and its role in tumor development are not well understood.
Purpose of the Study:
- To investigate the regulation of Foxp3 expression, particularly in response to DNA damage.
- To elucidate the role of the p53 pathway in controlling Foxp3 levels and function.
Main Methods:
- Utilized human breast and colon carcinoma cell lines with varying p53 statuses.
- Administered genotoxic agents (doxorubicin, etoposide) to induce DNA damage.
- Employed RNA interference to knock down p53 and Foxp3 expression.
- Assessed Foxp3 induction and p53-mediated growth inhibition.
Main Results:
- Foxp3 up-regulation upon DNA damage is dependent on functional p53.
- p53 directly regulates Foxp3 expression in response to genotoxic stress.
- Knockdown of p53 abolished Foxp3 induction, while p53 re-expression restored it.
- Foxp3 knockdown diminished the p53-mediated growth inhibitory effects.
Conclusions:
- Foxp3 induction during tumor suppression is controlled by p53 in a DNA damage-dependent manner.
- Foxp3 is a critical factor in determining cell fate within p53-mediated DNA damage responses.
- This highlights a novel regulatory axis in cancer cell response to DNA damage.
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