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Circadian Gating of the Mammalian Cell Cycle Restriction Point: A Mathematical Analysis

By Jing Su and Michael A. Henson, Senior Member, IEEE
Published July 13, 2015.

A critical decision in the mammalian cell cycle is whether to pass through the restriction point and enter the cell cycle. In this study, we modeled the decision making system of mammalian cell cycle entry and simulated circadian regulation of the restriction point driven by external epithelial growth factor (EGF) patterns. Our conceptual model replicated key signaling behaviors observed experimentally, suggesting the proposed network captured the essential system features. The model revealed the dramatic importance of EGF dynamics on promoting cell proliferation, showed that EGF signal duration was more important than signal strength for driving cells past the restriction point, and suggested that loss of circadian control of cell cycle entry could be associated with cancer development.

View the full article at IEEE Xplore

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