Semi-Disparate Impact of Kinases GCN2 and PERK in Modulating the Dynamic Control Properties of eIF2 Pathway

The tumor microenvironment associated with deficiencies in nutrients and oxygen is important in observing the regulation of tumor progression. The aggressiveness of the tumor cells can be stimulated by exposing it to nutrient starvation and hypoxia. During nutrient starvation, activation of an integrated stress response pathway takes place, which helps tumor cells to cope with nutrient stress. In this paper, an evolutionarily conserved central translational control pathway, i.e., the integrated stress response pathway is analyzed with the help of a mathematical model. This paper is of significant novelty in terms of testable predictions about specific pathway properties with the help of analysis tools from control theory. The investigation has suggested that both kinases GCN2 and PERK have semi-disparate impact on the dynamic control properties of the system. The examples include both kinases show analogous behavior toward the robustness and stability of the system, but disparate behavior in compensating the loss of another kinase