Computational Analysis of the Rb-E2F Pathway: Classification of Parameters
PublisherThe University of Arizona.
AbstractThe restriction point, or R-point, of the cell cycle behaves as a switch-like system which controls whether a cell progresses from the G1 phase to the S phase. The mechanism which controls the restriction point has been determined to be the Rb-E2F pathway. The Rb-E2F pathway is bistable; this allows for the system to exist in two states, ON or OFF, and explains the switch-like behavior observed in the R-point. The stimulus of this system is serum growth signal which exist at a concentration either low enough to keep the cells in a non-growing state called cellular quiescence or at a high level that activates the pathway into the ON state and commits the cell into proliferation. Yao et al. constructed a mathematical model to analyze the dynamics of the Rb-E2F pathway. The research of this paper involves the classification of the parameters used in this mathematical model to better understand similarities and differences of the components within the network's topology. Once classified, further analysis was performed with parameters that resulted in the decrease of bistable width. Only two phenotypes were observed from this analysis which suggests some potential evolutionary advantages of the bistable system.