Predicted Functions of MdmX in Fine-Tuning the Response of p53 to DNA Damage
Figure 7
Bifurcation diagram of the effects of MdmX on p53 oscillatory behavior.
Simulations were based on the model in Figure 2-A. The model includes p53-Mdm2 negative feedback loop (k33>0) without time delay and TR3 mediated positive feedback loop (k14>0). The black solid line represents steady state value of p53 activity as a function of basal production rate constant of p53. B1, B2, and B3 show bifurcation points. The steady state, surrounded by each curve (C1, C2, and C3) below the corresponding bifurcation point (B1, B2, and B3), was unstable, and the system oscillated between maximal and minimal p53 activity (species 14) indicated by each curve (C1, C2, and C3). Notably, a subcritical Hopf bifurcation was observed with k15 = 0.2, whereas supercritical Hopf bifurcations were observed when the value of k15 was 0 or 0.6. Solid curves C1, C2, C3 indicate stable limit cycles, and a dotted area in curve C2 indicates unstable limit cycles.