Modeling the roles of 14-3-3 σ and Wip1 in p53 dynamics and programmed cell death* *Project supported by the National Natural Science Foundation of China under Grant No. 11762011.

Abstract

The transcription factor p53, also known as the ‘guardian of the genome’ and the ‘gatekeeper’, encodes programmed cell death (apoptosis) information in its dynamics. The anti-cancer protein 14-3-3 σ and oncogenic protein Wild-type p53-induced phosphatase 1 (Wip1) are both in the p53-murine double minute 2 (Mdm2) gene network. However, how these two proteins modulate the dynamics of p53-Mdm2 module and further cell apoptosis remains elusive. Therefore, the authors constructed a relatively comprehensive ordinary differential equation model, taking into account the roles of 14-3-3 σ and Wip1 in p53 dynamics and cell apoptosis. By using numerical methods, we found that p53 exhibits abundant dynamics under the common control of 14-3-3 σ and Wip1, and explained the anti-apoptotic effect of Wip1 and the pro-apoptotic effect of 14-3-3 σ. By comparing experimental phenomena, we proposed that the p53 oscillation caused by the participation of Wip1 and 14-3-3 σ is closer to the real scene. This paper provides a new insight for p53 dynamics mechanism and apoptosis outcome mediated by Wip1 and 14-3-3 σ, and may be helpful for clinical application.