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

作　　者：苏瑞 李循[3] 王书恒 刘彼得 赵新军 李九智[3] SU Rui;LI Xun;WANG Shu-Heng;LIU Bi-De;ZHAO Xin-Jun;LI Jiu-Zhi(Xinjiang Laboratory of Phase Transitions and Microstructures in Condensed Matters,College of Physical Science and Technology,Yili Normal University,Yining 835000,China;Laboratory of Micro-Nano Electro Biosensors and Bionic Devices,Yili Normal University,Yining 835000,China;Department of Urology,the Xinjiang Uygur Autonomous Region People’s Hospital,Urumqi 830000,China)

机构地区：[1]伊犁师范大学物理科学与技术学院新疆凝聚态相变与微结构实验室,伊宁835000 [2]伊犁师范大学微纳电传感器技术与仿生器械实验室,伊宁835000 [3]新疆维吾尔自治区人民医院泌尿外科,乌鲁木齐830000

出　　处：《原子与分子物理学报》2024年第5期125-134,共10页Journal of Atomic and Molecular Physics

基　　金：国家自然科学基金(22163011);伊犁师范大学提升学科综合实力专项项目(22XKZY09)。

摘　　要：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.

关 键 词：Hes1蛋白 调控 AKT-MDM2-p53-PTEN通路 

分 类 号：Q492[生物学—生理学]