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. 2020 Apr 30;39(11):e104419. doi: 10.15252/embj.2020104419

Figure 9. Numerical Model for cyclin A and B specific and overlapping functions during mitotic entry and progression.

Figure 9

  1. Influence diagram of the network controlling the phosphorylation of mitotic substrates. The auto‐activation of CycB:Cdk1 and PP2A:B55 is controlled by inhibitory phosphorylation and by the Greatwall‐ENSA pathway, respectively. CycA:Cdk1 helps CycB:Cdk1 auto‐activation and inhibits PP2:B55 activity through Greatwall phosphorylation. Three different classes of mitotic substrates (early, intermediate and late) are distinguished based on their sensitivity to CycA:Cdk1, CycB:Cdk1 and PP2A:B55.
  2. Final level of mitotic regulators and Cdk1‐substrates in response to cyclin synthesis. The heat map is based on model simulations (C) starting with initial conditions without cyclins (interphase, top row) until high and constant cyclin levels caused by APC/C inhibition.
  3. Numerical simulation of mitotic substrate phosphorylation network in response to rising cyclin levels. The model simulates mitotic entry experiments where cyclin levels become stabilised by APC/C inhibition. Each row corresponds to one of the experimental conditions used in this work (control, CycA depletion etc.). Left columns: cyclin levels and phosphorylated mitotic substrates (early, intermediate and late). Right columns: temporal changes of some mitotic regulators. Changes of Cdc25‐P and Gwl‐P (not shown) are similar to phosphorylated ENSA (pENSA).