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

Abstract

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 \(\tau \)-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.

Graphic Abstract

The dynamics model of tumor suppressor p53 system is employed to investigate how PTEN protein mediates p53 dynamics after DNA damage and it indicates that the moderate p53-dependent PTEN synthesis rate is required for p53 to oscillate, while the higher p53-dependent PTEN synthesis rate is needed for the p53 bi-stable switch.

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Acknowledgements

The authors are very grateful to the reviewers for their constructive suggestions. This work was supported by the National Natural Science Foundation of China (Grant 11762011).

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Correspondence to Hongli Yang.

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Executive Editor: Ji-Zeng Wang.

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Liu, N., Yang, H., Li, S. et al. Oscillation and bistable switching dynamical behavior of p53 regulated by PTEN upon DNA damage. Acta Mech. Sin. (2021). https://doi.org/10.1007/s10409-020-01041-3

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Keywords

  • p53 dynamics
  • Phosphatase and tensin homolog
  • Bifurcation
  • Noise