Exploring the mechanism of the excitability of p53 pulse response

Abstract

DNA double-stranded breaks stimulate the digital pulse response of p53, which has the characteristic of excitability, and the mechanism of p53 pulse response has been extensively studied. However, the mechanism of the excitability of p53 pulse response remains to be elucidated. Here, we establish mathematical models of the p53 pulse response with different regulatory structures. Through simulation analysis and parameter space search, we find that the self-positive feedback of ATM can guarantee the excitability of p53 pulse response; We also analyze the effect of ATM-related parameters on the excitability of p53 pulse response. Our results are necessary for further exploring the mechanism of p53 pulse response and the cell fate decisions.