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Published on: June 6, 2017
Generation of oscillations by the p53-Mdm2 feedback loop: a theoretical and experimental study
R Lev Bar-Or1, R Maya, L A Segel
1Departments of Molecular Cell Biology and Applied Mathematics and Computer Science, The Weizmann Institute of Science, P. O. Box 26, 76100 Rehovot, Israel.
Summary
Mathematical modeling reveals that oscillations in p53 and Mdm2 protein levels can occur after cellular stress. This behavior, requiring a delay in Mdm2 induction, may enable DNA repair without continuous p53 activation.
Area of Science:
- Molecular Biology
- Cellular Dynamics
- Mathematical Modeling
Background:
- The p53 tumor suppressor protein's activity is tightly regulated by a feedback loop involving its target, mdm2.
- Understanding this regulatory mechanism is crucial for comprehending cellular responses to stress and potential cancer development.
Purpose of the Study:
- To investigate the potential for oscillations in p53 and Mdm2 protein levels in response to cellular stress.
- To explore the role of feedback loop dynamics, specifically time delays, in generating these oscillations.
Main Methods:
- Development of a simple mathematical model to simulate p53 and Mdm2 protein dynamics.
- Experimental validation using various cell types exposed to ionizing radiation.
Main Results:
- The mathematical model predicted that oscillations in p53 and Mdm2 levels can emerge under specific conditions, contingent on a delay in Mdm2 induction.
- Experimental results confirmed the occurrence of p53 and Mdm2 oscillations in cells treated with ionizing radiation, aligning with model predictions.
Conclusions:
- Oscillations in p53 and Mdm2 protein levels are a potential outcome of cellular stress responses.
- These oscillations may serve a biological role in facilitating DNA repair while preventing the detrimental effects of sustained high p53 activity.
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