Abstract

The intracellular activity of the p53 tumor suppressor protein is regulated through a feedback loop involving its transcriptional target, mdm2 . We present a simple mathematical model suggesting that, under certain circumstances, oscillations in p53 and Mdm2 protein levels can emerge in response to a stress signal. A delay in p53-dependent induction of Mdm2 is predicted to be required, albeit not sufficient, for this oscillatory behavior. In line with the predictions of the model, oscillations of both p53 and Mdm2 indeed occur on exposure of various cell types to ionizing radiation. Such oscillations may allow cells to repair their DNA without risking the irreversible consequences of continuous excessive p53 activation.

Keywords

Mdm2P53 proteinNegative feedbackSuppressorFeedback loopOscillation (cell signaling)Positive feedbackIntracellularDNA damagePhysicsLoop (graph theory)BiologyCell biologyControl theory (sociology)Computer scienceDNACell cultureCancerGeneticsGeneControl (management)EngineeringMathematicsVoltage

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Year
2000
Type
article
Volume
97
Issue
21
Pages
11250-11255
Citations
590
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Closed

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Ruth Lev Bar‐Or, Ruth Maya, Lee A. Segel et al. (2000). Generation of oscillations by the p53-Mdm2 feedback loop: A theoretical and experimental study. Proceedings of the National Academy of Sciences , 97 (21) , 11250-11255. https://doi.org/10.1073/pnas.210171597

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DOI
10.1073/pnas.210171597