H2AT120 蛋白磷酸化致癌的动力学特性

基于Hill动力学与Michaelis-Menten方程，建立理论模型研究H2AT120组蛋白磷酸化促进癌症发生发展的动力学特性.研究发现，在H2AubK119-H2AT120D-H2AT120P信号通路中，VRK激酶(vaccinia-related kinase 1)在很大程度上调控H2AT120磷酸化的动力学. VRK过高或者过低表达，都会促使H2AT120磷酸化出现异常，导致基因的不恰当表达，致使细胞癌变发生.通过考察体系演化过程中的动力学稳定性，我们发现，H2AubK119、H2AT120D、H2AT120P随时间演化动力学出现Hopf分岔，表明了体系随时间演化动力学的转变特性，由此也表明了，H2AT120蛋白磷酸化促进癌症发生发展的复杂性.基于本文模型，我们解释了VRK、H2AubK119、H2AT120D对致癌的调控特性，进一步理解了H2AubK119-H2AT120D-H2AT120P信号回路的致癌作用机理.理论结果符合实验，揭示了H2AT120磷酸化导致表观遗传变异的一种致癌机理，可为设计阻止由H2AT120发生变异诱发的癌症提供理论依据.

Kinetics of carcinogenesis caused by phosphorylation of H2AT120 protein

In this paper, based on Hill kinetics and Michaelis-Menten equation, we built a theoretical model to study the kinetics of H2AT120 protein phosphorylation to promote the oncogenic transformation. We found that in H2AubK119-H2AT120D-H2AT120P signaling pathway, the vaccinia-related kinase 1 (VRK1) regulates the kinetic behavior of H2AT120 protein phosphorylation. Overexpression or underexpression of VRK will cause abnormalities in the phosphorylation process of H2AT120, which leads to improper gene expression and oncogenic transformation. By investigating the dynamic stability of the H2AubK119-H2AT120D-H2AT120P signaling pathway system, we found that the H2AubK119, H2AT120D, and H2AT120P present Hopf bifurcation. It confirms the transition characteristics of the system''s evolutionary dynamics over time. This shows that the phosphorylation of H2AT120 protein promotes the complexity of cancer occurrence and development. Based on the model in this article, we explained the carcinogenic regulation characteristics of VRK, H2AT12 ubiquitination and [H2AT120D] mutation. The results can be used to further understood the carcinogenic mechanism induced by the H2AubK119-H2AT120D-H2AT120P signaling circuit. The theoretical results are consistent with the experiment, revealing a carcinogenic mechanism induced by epigenetic changes caused by phosphorylation of H2AT120 protein, which can provide a theoretical basis for the design to prevent cancers induced by histone mutations.