A skeleton model for the network of cyclin-dependent kinases driving the mammalian cell cycle

Abstract

We previously proposed a detailed, 39-variable model for the network of cyclin-dependent kinases (Cdks) that controls progression along the successive phases of the mammalian cell cycle. Here, we propose a skeleton, 5-variable model for the Cdk network that can be seen as the backbone of the more detailed model for the mammalian cell cycle. In the presence of sufficient amounts of growth factor, the skeleton model also passes from a stable steady state to sustained oscillations of the various cyclin/Cdk complexes. This transition corresponds to the switch from quiescence to cell proliferation. Sequential activation of the cyclin/Cdk complexes allows the ordered progression along the G1, S, G2 and M phases of the cell cycle. The 5-variable model can also account for the existence of a restriction point in G1, and for endoreplication. Like the detailed model, it contains multiple oscillatory circuits and can display complex oscillatory behaviour such as quasi-periodic oscillations and chaos. We compare the dynamical properties of the skeleton model with those of the more detailed model for the mammalian cell cycle.