Modeling the roles of 14-3-3 Σ and Wip1 in p53 dynamics and programmed cell death*

Nan Liu(刘楠),Hongli Yang(杨红丽),Liangui Yang(杨联贵)

Table 1. Simulation parameters.

Parameter Description Value and unit ATMt The total level of ATM 5 C kpatm Maximum activation rate of ATM 0.25 min−1 ρ0 The proportional weight of ATM* autocatalysis 0.96 – j0 Half-saturated concentration of ATM* autocatalysis 5 C kqatm Maximum inactivation rate of ATM 0.45 min−1 ρ1 The proportional weight of ATM* inactivation catalyzed by Wip1 0.95 – j1 Half-saturated concentration of Wip1 in the catalytic ATM* deactivation 0.9 C sp53 Basal production rate of p53 1.2 C · min−1 kqp53 Maximum inactivation rate of p53 0.8 min−1 ρ2 The proportional weight of p53* inactivation catalyzed by Wip1 0.91 – j2 Half-saturated concentration of Wip1 in the catalytic p53* deactivation 0.9 C kpp53 Maximum activation rate of p53 1 min−1 ρ3 The proportional weight of p53 activation catalyzed by ATM* 0.96 – j3 Half-saturated concentration of ATM* in the catalytic p53 activation 5 C dp53 Maximum degradation rate of p53 2.5 min−1 ρ4 The proportional weight of p53 degradation catalyzed by Mdm2 0.97 – j4 Half-saturated concentration of Mdm2 in the catalytic p53 degradation 1.5 C smdm2 Maximum generation rate of Mdm2 4.3 C·min−1 ρ5 The proportional weight of Mdm2 generation catalyzed by p53* 0.95 – j5 Half-saturated concentration of p53* in the catalytic Mdm2 generation 1.5 C kqmdm2 Maximum dephosphorylation rate of Mdm2 3 min−1 ρ6 The proportional weight of Mdm2* dephosphorylation catalyzed by Wip1 0.98 – j6 Half-saturated concentration of Wip1 in the catalytic Mdm2* dephosphorylation 0.9 C kpmdm2 Maximum phosphorylation rate of Mdm2 2.5 min−1 ρ7 The proportional weight of Mdm2 phosphorylation catalyzed by ATM* 0.96 – j7 Half-saturated concentration of ATM* in the catalytic Mdm2 phosphorylation 5 C dmdm2 Maximum degradation rate of Mdm2 1.03 min−1 ρ8 The proportional weight of Mdm2 degradation catalyzed by 14-3-3 Σ 0.93 – j8 Half-saturated concentration of 14-3-3 Σ in the catalytic Mdm2 degradation 0.7 C swip1 Maximum synthesis rate of Wip1 0.16 C·min−1 ρ9 The proportional weight of Wip1 generation catalyzed by p53* 0.95 – j9 Half-saturated concentration of p53* in the catalytic Wip1 generation 0.35 C dwip1 Basal degradation rate of Wip1 0.013 min−1 s14-3-3 Σ Maximum synthesis rate of 14-3-3 Σ 0.5 C·min−1 ρ10 The proportional weight of 14-3-3 Σ generation catalyzed by p53* 0.99 – j10 Half-saturated concentration of p53* in the catalytic 14-3-3 Σ generation 0.4 C d14-3-3 Σ Basal degradation rate of 14-3-3 Σ 0.175 min−1 k1 The ratio of p53* to p53 degradation rate 0.1 – k2 The ratio of Mdm2* to Mdm2 degradation rate 10 -