Fig 2. A model for mitotic entry shows how dynamic switches appear in two cellular compartments.

A) The core protein interaction network involved in mitotic entry with double positive and double negative feedback loops centered on the Cyclin B-Cdk1 complex. Additional feedbacks act on the import rates of Cdc25 and Cyclin B-Cdk1. B) Two cellular compartments can exchange proteins through import and export. The total concentration of Cdc25 in each compartment determines the shape of the bistable response, which changes over time. C) Time series of active Cdk1 in nucleus and cytoplasm, from a simulation of mitotic entry driven by Cyclin B production in the cytoplasm. The vertical lines correspond to the different response curves in Panel D. D) Left: initially the activation threshold in the nucleus lies to the far right, due to the dominance of Wee1 over Cdc25 there. The activation threshold shifts to the left as Cdc25 is imported, which happens faster as Cdk1 activity rises in the cytoplasm. Middle: the activation threshold for Cdk1 activation is first crossed in the cytoplasm. The sudden jump in Cdk1 activation effects a sudden increase of Cdc25 import into the nucleus, which in turn quickly lowers the activation threshold there. Right: the decrease of the threshold in the nucleus triggers activation of Cdk1, leading to additional import of Cyclin B and a high Cdk1 activity. The black dot denotes the position of the system, the black curve corresponds to the bistable response at the time point corresponding to the dot. The gray lines are snapshots of the bistable response at times leading up to this point, corresponding to the time points indicated in Panel C. An animation which more clearly illustrates the dynamics can be found in S4 Video.