Taking the interaction between a DNA damage repair module, an ATM module, and a P53--MDM2 oscillation module into account, this paper presents a mathematical model of a P53 oscillation network triggered by a DNA damag...Taking the interaction between a DNA damage repair module, an ATM module, and a P53--MDM2 oscillation module into account, this paper presents a mathematical model of a P53 oscillation network triggered by a DNA damage signal in individual cells. The effects of the DNA damage signal and the delay time of P53-induced MDM2 expression on the behaviours of the P53 oscillation network are studied. In the oscillatory state of the P53--MDM2 oscillator, it is found that the pulse number of P53--P oscillation increases with the increase of the initial DNA damage signal, whereas the amplitude and the period of P53--P oscillation are fixed for different initial DNA damage signals, and the period numbers of P53--P oscillations decrease with the increase of time delay of MDM2 expression induced by P53. These theoretical predictions are consistent with previous experimental results. The combined negative feedback of P53--MDM2 with the time delay of P53-induced MDM2 expression causes oscillation behaviour in the P53 network.展开更多
基金Project supported by the National Natural Science Foundation of China (Grant No. 10875049)the Key Project of Chinese Ministry of Education (Grant No. 108096)the Programme of Introducing Talents of Discipline to Universities (Grant No. B08033)
文摘Taking the interaction between a DNA damage repair module, an ATM module, and a P53--MDM2 oscillation module into account, this paper presents a mathematical model of a P53 oscillation network triggered by a DNA damage signal in individual cells. The effects of the DNA damage signal and the delay time of P53-induced MDM2 expression on the behaviours of the P53 oscillation network are studied. In the oscillatory state of the P53--MDM2 oscillator, it is found that the pulse number of P53--P oscillation increases with the increase of the initial DNA damage signal, whereas the amplitude and the period of P53--P oscillation are fixed for different initial DNA damage signals, and the period numbers of P53--P oscillations decrease with the increase of time delay of MDM2 expression induced by P53. These theoretical predictions are consistent with previous experimental results. The combined negative feedback of P53--MDM2 with the time delay of P53-induced MDM2 expression causes oscillation behaviour in the P53 network.
