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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
The ARF/oncogene pathway activates p53 acetylation within the DNA binding domain
Hestia Mellert1, Stephen M Sykes, Maureen E Murphy
1Biomedical Graduate Studies, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Cell Cycle (Georgetown, Tex.)
|May 31, 2007
Summary
Cellular stress stabilizes the p53 tumor suppressor through distinct pathways. Both DNA damage and oncogene activation pathways induce acetylation of p53 at lysine 120, a critical modification for its tumor-suppressing function.
Area of Science:
- Molecular Biology
- Cellular Biology
- Cancer Research
Background:
- p53 tumor suppressor stabilization is crucial for cellular stress response.
- Two pathways, DNA damage response and p19ARF/oncogene activation, mediate p53 stabilization.
- The p19ARF pathway's impact on p53 post-translational modifications is less understood compared to the DNA damage pathway.
Purpose of the Study:
- To investigate the post-translational modifications of p53 induced by different cellular stress pathways.
- To determine if the p19ARF pathway, similar to the DNA damage pathway, affects p53 modification.
- To confirm the role of p53 acetylation at lysine 120 in response to oncogene-induced stress.
Main Methods:
- Analysis of p53 modifications in response to genotoxic stress.
- Investigation of p53 stabilization and modification following oncogene activation and p19ARF induction.
- Site-specific analysis of p53 acetylation at lysine 120.
Main Results:
- Both DNA damage response and p19ARF/oncogene stress pathways lead to p53 stabilization.
- Acetylation of p53 at lysine 120 is induced by both pathways.
- This specific acetylation event is essential for p53's tumor-suppressive apoptotic function and is impaired in tumor-derived mutations.
Conclusions:
- Acetylation of p53 at lysine 120 is a common modification event occurring via both DNA damage and oncogene stress response pathways.
- This modification is a key mechanism linking cellular stress to p53's tumor suppressor activity.
- Understanding this conserved modification provides insights into cancer development and potential therapeutic strategies.
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