Oscillation and bistable switching dynamical behavior of p53 regulated by PTEN upon DNA damage

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The tumor suppressor p53 plays a key regulatory role in the response of cells to various stresses.It have experimentally shown that p53 can exhibit rich dynamic behaviors under DNA damage.In order to study the meticulous mechanism,we construct a coupling model including p53-murine double minute 2(Mdm2)negative feedback loop(NFL)and p53-phosphatase and tensin homolog(PTEN)-Mdm2 positive feedback loop(PFL).By making use of bifurcation analysis and Binomial r-leap algorithm,we confirm that PTEN is a essential condition for p53 oscillation or bistable switching dynamic behaviours.We investigate the p53 dynamics affected by PFL through studying the p53-dependent PTEN synthesis rate.The results suggest that PFL may enrich the dynamic behaviors of the p53 system.This work can promote the understanding of p53 dynamics mediated by PTEN and provide clues for cancer therapy.
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