Fig 2: Revised model of the Cdk1 activation loop.The regulation of Gwl dephosphorylation by PP2A/B55 and Ensa/ARPP19 dephosphorylation by Fcp1 are incorporated into the previous network shown on Fig. 1A. Since Fcp1 is inhibited in Cdk1 dependent manner, Ensa is regulated by a coherent feed-forward loop as well: Cdk1 both activates the phosphorylation (via Gwl) and inhibits the dephosphorylation (via Fcp1) of Ensa.

Fig 3: The regulatory network and the dynamics of the mitotic switch.(A) Model of the Cdk1 activation switch. Cdk1 activity is regulated by inhibitory Tyr15 phosphorylation modulated through the activities of Wee1 and Cdc25. The activity of these modifying enzymes are regulated both directly and indirectly (through Gwl, Ensa/ARPP19 and PP2A/B55) by Cdk1. (B–J) Simulation of mitotic entry and exit using a mathematical model of the regulatory network with the assumption included that Gwl is dephosphorylated by an OA-insensitive phosphatase (left panels), by an OA-sensitive phosphatase (middle panels), or specifically by PP2A/B55 (right panels). The simulation of mitotic entry is shown from the initial condition obtained using Cdk1 inhibition and either removal of Cdk1 inhibition (B–D) or PP2A inhibition by OA (E–G) promotes mitotic entry. The mitotic exit (H–J) is shown from the initial condition corresponding to metaphase state and Cdk1 inhibition promotes mitotic exit.