Figure 3
Dynamical analysis of fractional killing. (A) One parameter bifurcation analysis for the activation of BAXm by p53. The black curve indicates BAXm level as a function of the level of p53. At low levels of p53, BAXm is inactivated; after the level of p53 increases over the threshold (black θ), BAXm is activated. The blue curve indicates the elevated BAXm threshold (blue θ) after the level of CIAP is increased. (B) Time series simulation of an apoptotic cell. In this cell, p53 (black curve) is activated early, when the level of CIAP (blue curve) is low. As a result, BAXm (red curve) is activated. (C) Time series simulation of a surviving cell. In this cell, p53 is activated after CIAP levels have already increased. Hence, BAXm remains inactive. (D) Two parameter bifurcation analysis with p53 and CIAP as control parameters. The black curve indicates the threshold of BAXm activation. At the right of this black solid curve, BAXm is activated and the cell undergoes apoptosis (labelled as “apoptosis”). The black dashed curve indicates the threshold of BAXm inactivation, at the left of this dashed curve, BAXm is inactive and the cell survives (labelled as “survival”). Between the solid and the dashed curve, is the predicted hysteretic area. The red and blue curves indicate the time dependent trajectories of the apoptotic and the surviving cells, as shown in (B and C).
