To better understand the dynamics of the complex biochemical networks controlling the initiation of cell cycle, which is of critical importance for cancer, I initiated an analysis of simple mathematical models representing the characteristic features of the G1/S phase transition in mammalian cells. We developed a mathematical model based on the hypothesis that the phosphorylation of pRb family proteins complexed with E2F family of proteins leads to release of free active E2F thus activating the synthesis of proteins required for the cell cycle progression, including cyclin E which forms a positive feedback ensuring the irreversible passage through the restriction point. The solution of the five differential equations describing this model represented the characteristic features of a trigger system with a positive feedback. The concentration of E2F rose after the application of the external trigger but gradually declined in the absence of a positive feedback; however, in the presence of a positive feedback provided by the increased concentration of cyclin E, the concentration of E2F did not decline after removing the external trigger but resumed a relatively high quasi-steady state level. Currently, we are analyzing more sophisticated models and proposing experiments based on those models. Z01 BC 10042-02 LMMB to LECB
