Dynamics of the p53-Mdm2 feedback loop in individual cells
Dynamics of the p53-Mdm2 feedback loop in individual cells
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DOI：
10.1038/ng1293
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发表时间：
2004-02-01
期刊：
影响因子：
30.8
通讯作者：
Alon, U
中科院分区：
文献类型：
--
作者：
Lahav, G;Rosenfeld, N;Alon, U
肿瘤抑制因子p53是研究最深入的蛋白之一（1-5），通常通过在细胞群中平均的实验来研究，可能掩盖单个细胞中的动态行为。我们提出了一个系统来跟踪，在单个活细胞中，p53及其负调节Mdm2的动态（参考文献）。1, 4-7)：该系统使用功能性p53-CFP和Mdm2-YFP融合蛋白和延时荧光显微镜。我们发现p53在DNA损伤后以一系列离散脉冲表达。基因相同的细胞有不同数量的脉冲：0、1、2或更多。每次脉冲的平均高度和持续时间是固定的，不依赖于DNA损伤的数量。然而，脉冲的平均次数随着DNA损伤而增加。这种方法可以用于研究其他信号系统，并表明p53- mdm2反馈回路产生一个数字时钟，释放p53的定时量子，直到损伤被修复或细胞死亡。
The tumor suppressor p53, one of the most intensely investigated proteins(1-5), is usually studied by experiments that are averaged over cell populations, potentially masking the dynamic behavior in individual cells. We present a system for following, in individual living cells, the dynamics of p53 and its negative regulator Mdm2 (refs.1, 4-7) : this system uses functional p53-CFP and Mdm2-YFP fusion proteins and time-lapse fluorescence microscopy. We found that p53 was expressed in a series of discrete pulses after DNA damage. Genetically identical cells had different numbers of pulses: zero, one, two or more. The mean height and duration of each pulse were fixed and did not depend on the amount of DNA damage. The mean number of pulses, however, increased with DNA damage. This approach can be used to study other signaling systems and suggests that the p53-Mdm2 feedback loop generates a digital clock that releases well-timed quanta of p53 until damage is repaired or the cell dies.