Hes1调控AKT-MDM2-p53-PTEN通路的一种物理机制

A physical mechanism of Hes1 regulating AKT-MDM2-p53-PTEN pathway

基于Hill动力学与Michaelis-Menten方程,建立理论模型研究发状分裂相关增强子1(Hairy and enhancer of split 1,Hes1)调控蛋白激酶B(Protein Kinase B,AKT)-鼠双微体2(Murine Double Minute2,MDM2)-抗癌基因p53(p53)-第10号染色体缺失的磷酸酶及张力蛋白同源的基因(Phosphatase and tensin homolog deleted on chromosome ten,PTEN)通路的一种物理机制.研究发现,Hes1通过与PTEN结合抑制PTEN表达,并调控AKT信号.表明了Hes1蛋白的合成,以及Hes1与PTEN相互作用调控AKT-MDM2-p53-PTEN通路信号,将会有效地控制细胞结果.Hes1作为AKT-MDM2-p53-PTEN信号通路中上游调节的重要因素,还可以在一定程度上通过影响p53蛋白功能,改变p53对肿瘤的抑制性.理论结果可用于预测Notch通路信号异常诱导的致癌性,并进一步揭示了Notch信号通路影响细胞AKT-MDM2-p53-PTEN通路的激活机制.

Based on Hill dynamics and Michaelis Menten equation,a theoretical model was established to study a physical mechanism of hairy and enhancer of split 1(Hes1)regulating Protein Kinase B(AKT)-Murine Double Minute2(MDM2)-p53-phosphatase and tensin homolog deleted on chromosome ten(PTEN)pathway.We found that HES1 inhibits the expression of PTEN and regulates AKT signal by combining with PTEN.It shows that the kinetics of Hes1 protein synthesis and the interaction between Hes1 and PTEN to regulate AKT-MDM2-p53-PTEN pathway signal will effectively control cell results.As an important factor in upstream regulation of AKT-MDM2-p53-PTEN signal pathway,Hes1 can also change the inhibition of p53 on tumor by affecting the function of p53 protein to a certain extent.The theoretical results can be used to predict the carcinogenicity induced by abnormal Notch signal pathway,and further reveal the mechanism of Notch signal pathway affecting the activation of AKT-MDM2-p53-PTEN pathway in cells.