Generation of oscillations by the p53-Mdm2 feedback loop: A theoretical and experimental study

The intracellular activity of the p53 tumor suppressor protein is regulated through a feedback loop involving its transcriptional target, mdm2, We pre sent a simple mathematical model suggesting that under certain circumstance s, 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 b e required, albeit not sufficient for this oscillatory behavior. In line wi th the predictions of the model, oscillations of both p53 and Mdm2 indeed o ccur on exposure of various cell types to ionizing radiation. Such oscillat ions may allow cells to repair their DNA without risking the irreversible c onsequences of continuous excessive p53 activation.