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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Three optimized assays for the evaluation of compounds that can rescue p53 mutants
Jiale Wu1, Huaxin Song1, Zhengyuan Wang1
1Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine (Shanghai), Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Abstract:
Identifying drugs targeting p53 remains a major focus of precision oncology, with over twenty compounds that can rescue p53 mutants reported. Here, we suggest three easily accessible assays to determine the thermostability, protein folding, and transcriptional activity of p53 mutants-the go-to criteria for evaluating a rescue compound that acts by increasing p53 thermostability. Because of the diversity of p53 mutants, a compound that meets the criteria of one assay does not necessarily meet the criteria of the other assays. For complete details on the use and execution of this protocol, please refer to Chen et al. (2021).
Insights
Researchers present three accessible assays to evaluate p53 mutant rescue compounds. These tests assess protein thermostability, folding, and transcriptional activity, crucial for precision oncology drug development.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Targeting p53 mutants is a key strategy in precision oncology.
- Over twenty compounds have been reported to rescue p53 mutants.
- Evaluating these compounds requires robust assessment criteria.
Purpose of the Study:
- To propose three accessible assays for evaluating p53 mutant rescue compounds.
- To establish criteria for assessing compounds that enhance p53 thermostability.
- To highlight the importance of comprehensive evaluation due to p53 mutant diversity.
Main Methods:
- Thermostability assay to measure compound effects on p53 protein stability.
- Protein folding assay to assess the structural integrity of p53 mutants.
- Transcriptional activity assay to determine the functional restoration of p53.
Main Results:
- The study outlines three distinct assays for p53 mutant rescue compound evaluation.
- Demonstrates that a compound's efficacy can vary across different assays.
- Emphasizes that meeting criteria in one assay does not guarantee efficacy in others.
Conclusions:
- These assays provide a standardized approach to evaluating p53 rescue compounds.
- Comprehensive testing is essential for identifying effective precision oncology drugs.
- The diversity of p53 mutants necessitates multi-faceted compound assessment.
