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

• 作者: Nan Liu Hongli Yang Liangui Yang
• 来源期刊: 理论物理通讯（英文版）
• 年，卷（期）: 2021,（8）
• 所属期刊栏目: STATISTICAL PHYSICS,SOFT MATTER AND BIOPHYSICS
• 页码范围: 160-170
• 页数: 11页
• 语种: 英文

摘要

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 14-3-3σ.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.