Generation of oscillations by the p53-Mdm2 feedback loop: A theoretical and experimental study
Generation of oscillations by the p53-Mdm2 feedback loop: A theoretical and experimental study
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DOI：
10.1073/pnas.210171597
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发表时间：
2000-10-10
影响因子：
11.1
通讯作者：
Oren, M
中科院分区：
文献类型：
--
作者：
Bar-Or, RL;Maya, R;Oren, M
p53肿瘤抑制蛋白的细胞内活性是通过涉及其转录靶点mdm2的反馈环来调节的。我们提出了一个简单的数学模型，表明在某些情况下，p53和Mdm 2蛋白水平的振荡可以响应于应激信号而出现。预测需要延迟Mdm2的p53依赖性诱导，尽管对于这种振荡行为是不够的。与模型的预测一致，p53和Mdm 2的振荡确实发生在各种细胞类型暴露于电离辐射时。这种振荡可能允许细胞修复它们的DNA，而不会冒着持续过度激活p53的不可逆后果的风险。
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.