Deciphering p53 dynamics and cell fate in DNA damage response using mathematical modeling

Abstract

The tumor suppressor p53 is activated in response to cellular stresses. The transcription factor p53 can activate the expression of numerous genes leading to cell cycle arrest, senescence or apoptosis. The p53 network exhibits complex stimulus-dependent dynamics under stressed and non-stressed conditions. Mathematical models contribute significantly to enhanced understanding of p53 network topology. In this review, we discuss the evolution of kinetic p53 modeling, multiple mechanisms for distinct p53 dynamics, and how the temporal p53 dynamics determine cell fate over the last 2 decades. The Information encoding and decoding strategies through p53 signaling network enable cells to undergo appropriate cellular outcomes.

Funding

National Key Research and Development Program of China(2017YFA0506000); National Key Research and Development Program of China(2017YFA0205400); National Natural Science Foundation of China(31971185)