Boolean model of growth signaling, cell cycle and apoptosis predicts the molecular mechanism of aberrant cell cycle progression driven by hyperactive PI3K
Fig 8
p110 degradation in G2 is required for cytokinesis.
(A) Top: Molecular mechanism leading to the failure of cytokinesis in the presence of non-degradable p110H. Blue background: lower than normal activity; no background: other relevant node / process; →: activation; ⊣: inhibition. Bottom: Dynamics of regulatory molecule activity during the transition from cell cycle to telophase, then genome duplication upon expression of non-degradable p110 (yellow). X-axis: time-steps; y-axis: nodes of the model organized in modules; orange/blue: ON/OFF; yellow: ON, forcibly expressed; white arrows & nodes: factors driving Plk1 expression and lack of Plk1H accumulation; red arrows & box: failure of cytokinesis followed by G1 in bi-nucleated cells; only relevant module activity is shown (full dynamics available in S1 File). (B-C) Relative occurrence of normal cell cycle completion (mustard) vs. genome duplication following failed cytokinesis (blue) relative to the rate of cell cycle in wild-type cells (stacked bar charts) at 80% growth factor exposure in cells with non-degradable p110H (top), non-degradable p110H + active PI3KH (middle) and hyperactive AKTH (bottom). Modeled using synchronous (B) and biased asynchronous update (C).