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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. [ABSTRACT FROM AUTHOR]

Based on Hill kinetics and Michaelis - Menten function, we investigate Nogo - Band JCAD inducing activation of hepatocellular carcinoma(HCC) gene. The theoretical model considers : (1) Nogo - B promotes the degradation of oxidized low density lipoprotein (ox LDL) by interacting with Autophagy - related 5 gene (ATG5), and the degraded oxLDL(DoxLDL) enhances the Yes - associated protein (YAP) activity in Hippo signaling pathway, which activates the expression of oncogenes(connective tissue growth factor (CTGF)) by promoting the production of a large amount of Lysopho - sphatidic acid (LPA); (2) JCAD interacts with large tumor suppressor homolog 2 (LATS2) to regulate phosphorylation of YAP. Dephosphorylated YAP activates tumor - related proliferation factors in the Hippo signaling pathway, in turn upregulating activation of YAP to promote HCC cell proliferation. We found that ox LDL degrades in a short time. The degradation of oxLD L promotes LPA largely, and then promotes the activation of YAP in Hippo signaling pathway. During this process, DoxLDL will quickly activate a large number of inactivated cascade path signals ( ( Lysophosphatidylcholine ( LPC), auto- taxin( ATX), LPA, etc. ), which activate expression of HCC gene. By analyzing the temporal evolutions of the levels of Nogo - B, it can be found that Nogo - Band ATG5 forms a complex NA. The ATG5 amplifies the signal of Nogo - B expression. It makes Nogo - B - enhanced activation expression, which promotes LPA production and activates YAP. A pulsed signal driven by the CEBPJ3 will also enhance the transcriptional activation of Nogo - B. The YAP and CTGF showed a steady state with the change of Nogo - B. This indicates further that oxLDL degradation induced by up - regulation of Nogo - B expression activates the stable oxLDL - Nogo - B - YAP - CTGF pathway. Hippo signaling is highly activated after ectopic Nogo - B expression. By analyzing the regulatory effects with the JACD and kinase LATS2, we found that JACD inhibits YAP phosphorylation, which greatly increases the expression level of CTGF. It is opposite to the effect of JCAD regulation, LATS2 promotes YAP phosphorylation, and then decreases the expression of CTGF and other proliferation factors. Our theoretical results are consistent with the experimental observations, and provide a fundamental understanding of the Non - alcoholic steatohepatitis ( NASH) inducing HCC [ABSTRACT FROM AUTHOR]

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