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Updated: Aug 19, 2026
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Pilot screening programme for small molecule activators of p53
Rachel G Berkson1, Jonathan J Hollick, Nicholas J Westwood
1Department of Surgery and Molecular Oncology, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, United Kingdom.
Abstract:
Activation of the p53 tumour suppressor is predicted to have therapeutically beneficial effects. Many current anti-cancer therapies activate the p53 response via DNA damage. Non-genotoxic activation of the p53 pathway would open the way to long-term and possibly prophylactic treatments. We have established a simple protocol to screen small compound libraries for activators of p53-dependent transcription, and to select and characterise the most interesting hits, which include non-genotoxic activators. These compounds or their derivatives are of potential clinical interest. This approach may also lead to the identification of novel p53-activating compound families and possibly to the description of novel molecular pathways regulating p53 activity.
Insights
Researchers developed a new method to screen for compounds that activate the p53 tumor suppressor pathway without causing DNA damage. This discovery could lead to new long-term cancer treatments and prophylactic therapies.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- The p53 tumor suppressor is crucial in cancer, and its activation has therapeutic potential.
- Current cancer therapies often rely on DNA damage to activate p53.
- Non-genotoxic activation of p53 offers possibilities for long-term and prophylactic cancer treatments.
Purpose of the Study:
- To establish a screening protocol for identifying p53-dependent transcriptional activators.
- To discover novel non-genotoxic compounds that activate the p53 pathway.
- To explore potential clinical applications and new molecular pathways regulating p53.
Main Methods:
- Development of a simple protocol for screening small compound libraries.
- Identification and characterization of compounds activating p53-dependent transcription.
- Focus on non-genotoxic activators.
Main Results:
- Successfully established a screening protocol for p53 activators.
- Identified several small compounds that activate p53-dependent transcription.
- Discovered non-genotoxic activators with potential clinical interest.
Conclusions:
- The developed screening protocol is effective for identifying p53 activators.
- Non-genotoxic p53 activators represent promising candidates for cancer therapy.
- This approach may uncover novel p53-activating compounds and regulatory pathways.
