Dynamic Modelling and Simulation of the Hypoxia-Inducible Factor 1 (HIF-1) SUMOylation in Response to Hypoxia

Hypoxia, low oxygen level in tissues, is encountered in both physiological processes and pathological situations, such as ischemia and cancer. Recent experimental data have shown that protein post-translational modifications (PTMs), in particular SUMOylation, play crucial roles in cellular response to hypoxia. In this study, we develop a mathematical model of SUMOylation-dependent synergism of hypoxia response to gain a better understanding of how HIF interacts with SUMO proteins to sense oxygen and respond to hypoxia. The primary result shows the effect of oxygen concentration on SUMO conjugation level. Clinical Relevance— This result has implications for cancer treatment by using model prediction to drug treatment under varying degrees of hypoxia.