Progression along the successive phases of the mammalian cell cycle is driven by a
network of cyclin-dependent kinases (Cdks). This network is regulated by a variety of
negative and positive feedback loops. We previously proposed a detailed, 39-variable model
for the Cdk network and showed that it is capable of temporal self-organization in the
form of sustained oscillations, which correspond to the repetitive, transient, sequential
activation of the cyclin- Cdk complexes that govern the successive phases of the cell
cycle [Gérard and Goldbeter (2009) Proc Natl Acad Sci 106, 21643-8]. Here we compare the
dynamical behavior of three models of different complexity for the Cdk network driving the
mammalian cell cycle. The first is the detailed model that counts 39 variables and is
based on Michaelis-Menten kinetics for the enzymatic steps. From this detailed model, we
build a version based only on mass-action kinetics, which counts 80 variables. In this
version we do not need to assume that enzymes are present in much smaller amounts that
their substrates, which is not necessarily the case in the cell cycle. We show that these
two versions of the model for the Cdk network yield similar results. In particular they
predict sustained oscillations of the limit cycle type. We show that the model for the Cdk
network can be reduced to a version containing only 5 variables, which is more amenable to
stochastic simulations. This skeleton version retains the dynamic properties of the more
complex versions of the model for the Cdk network in regard to Cdk oscillations. The
regulatory wiring of the Cdk network therefore governs its dynamic behavior, regardless of
the degree of molecular detail. We discuss the relative advantages of each version of the
model, all of which support the view that the mammalian cell cycle behaves as a limit
cycle oscillator.