广西医科大学研究生学院;四川省肿瘤医院(放疗科),四川省肿瘤医院放疗科
国家自然科学基金(11375124)和四川省自然科学基金(2013JY0106)资助项目
Guangxi Medical University ;Sichuan Cancer Hospital,Sichuan Cancer Hospital
This work was supported by grants from The National Natural Science Foundation of China(11375124) , Natural Science Foundation of Sichuan Province(2013JY0106)
P53脉冲是指细胞内p53蛋白水平周期性或重复性的涨落.该脉冲产生的途径是调节p53的各种正负反馈环,其核心的两个负反馈环是p53-Mdm2环和Wip1-ATM-p53环.这些负反馈环能产生极限环振荡,在极限环振荡区,P53水平成脉冲型变化.随着P53脉冲的增多,不同形式的p53蛋白和促凋亡蛋白逐渐积累并到达一定阈值水平,可打开凋亡“开关”,引发不可逆的细胞命运.除了P53脉冲的数目,其频率、振幅、波形等物理学参数也与细胞命运存在密切关系.这一研究进展对阐明诸多疾病发生机理和防治研究有重要意义.
P53 pulses refer to the fluctuation of the p53 protein levels in the cells in a periodic or repetitive manner. The mechanisms for triggering P53 pulses lie in several kinds of the positive and negative feedback loops in the p53 network. Two core feedback loops include the p53-Mdm2 negative feedback loop and Wip1-ATM-p53 negative feedback loop. Owing to the existence of these feedback loops, a limit cycle and a given number of P53 pulses were generated when the p53 system entered the limit cycle region. Pro-apoptotic regulator and P53 existing in different form are gradually accumulated as the number of P53 pulses increases and then the irreversible cell fate is determined by opening apoptotic "switch" above the threshold level. The cell fate can be determined by the number of P53 pulses partly, but it also has close relationship with its frequency, amplitude and wave form. Therefore, it is of great significance for the mechanism investigation of diseases development, prevention and treatment.
曹志,王卫东. P53脉冲的研究现状与展望[J].生物化学与生物物理进展,2015,42(2):147-153
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