A death-survival switch in cell: cross talk between Akt and p53

摘要

A dynamical model for the p53-Mdm2 feedback loop regulated by Akt is reported in this work. By computational simulation, it reproduces the stable oscillatory pulses in p53-Mdm2 negative feedback loop which is functionally responsible for cell repair or apoptosis in individual cell. With the survival stress, in the tumor suppressor-oncoproteins networks, the model indicates the potential to exhibit the oscillation-stationary state bifurcation for the kinetics of p53, and the death-survival switch in the p53-Akt cross talk which somehow leads cell to either programmed apoptosis or survival. It's found that low Akt activation is speculated to p53 normally holding the response to cellular repair or apoptosis, but large Akt amount keeping a high Akt activation restricts p53 at a low expression level and engenders malfunctions in cellular repair or apoptosis so that the cell survives with potential probability to cancer or mutation.