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Role for p300 in stabilization of p53 in the response to DNA damage
1Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Abstract:
The nuclear p300/CBP proteins function as coactivators of gene transcription. Here, using cells deficient in p300 or CBP, we show that p300, and not CBP, is essential for ionizing radiation-induced accumulation of the p53 tumor suppressor and thereby p53-mediated growth arrest. The results demonstrate that deficiency of p300 results in increased degradation of p53. Our findings suggest that p300 contributes to the stabilization and transactivation function of p53 in the cellular response to DNA damage.
Insights
The protein p300, not CBP, is crucial for stabilizing the p53 tumor suppressor after radiation. p300 deficiency increases p53 degradation, impacting DNA damage response and growth arrest.
Area of Science:
- Molecular biology
- Cancer research
- Cellular response to DNA damage
Background:
- The nuclear proteins p300 and CBP act as transcriptional coactivators.
- Gene transcription regulation is vital for cellular function and response to stimuli.
- The p53 tumor suppressor plays a critical role in cell cycle control and apoptosis.
Purpose of the Study:
- To investigate the distinct roles of p300 and CBP in the cellular response to ionizing radiation.
- To determine the specific coactivator essential for p53 accumulation and function following DNA damage.
- To elucidate the mechanism by which p300 influences p53 stability and activity.
Main Methods:
- Utilizing cell lines deficient in either p300 or CBP.
- Exposing these cells to ionizing radiation.
- Analyzing the accumulation and degradation of the p53 tumor suppressor.
- Assessing p53-mediated growth arrest.
Main Results:
- p300, but not CBP, was found to be essential for the accumulation of p53 after ionizing radiation exposure.
- Cells deficient in p300 exhibited increased degradation of p53.
- The absence of p300 impaired p53-mediated growth arrest.
Conclusions:
- p300 plays a critical role in stabilizing the p53 tumor suppressor in response to DNA damage.
- p300 is required for the transactivation function of p53, contributing to cellular responses like growth arrest.
- These findings highlight a specific function of p300 in DNA damage signaling pathways.