Modeling and Evaluating the Cdc2 and Cyclin Interactions in the Cell Divison Cycle with a Time Dependent Petri Net – A Case Study

Figure 1: In step 1, cyclin is synthesized de novo. Newly synthesized cyclin may be unstable (step 2). Cyclin combines with cdc2-P (step 3) to form pre-maturation promoting factor (preMPF). At some point after heterodimer formation, the cyclin subunit is phosphorylated. ... The cdc2 subunit is then dephosphorylated (step 4) to form active MPF. In principle, the activation of MPF may be opposed by protein kinase (step 5). Assuming that active MPF enhances the catalytic activity of the phosphatase, I arrange that MPF activation is switched on in an autocatalytic fashion. Nuclear division is triggered when a sufficient quantity of MPF has been activated, but concurrently active MPF is destroyed by step 6. Breakdown of the MPF complex releases phosphorylated cyclin, which is subject to rapid proteolysis (step 7). Finally, the cdc2 subunit is phosphorylated (step 8, possibly reversed by step 9), and the cycle repeats itself. (Tyson, J.J.)