Roles of cellular heterogeneity, intrinsic and extrinsic noise in variability of p53 oscillation.

ABSTRACT: The p53 protein is a key mediator of the cellular response to various stress signals. In response to DNA damage, the concentration of p53 can temporally oscillate with fluctuations in both the amplitude and period. The underlying mechanism for p53 variability is not fully understood. Here, we construct a core regulatory network of p53 dynamics comprising the ATM-p53-Wip1 and p53-Mdm2 negative feedback loops. We dissect the contributions of cellular heterogeneity, intrinsic noise, and multiple forms of extrinsic noise to p53 variability in terms of the coefficients of variation of four quantities. Cellular heterogeneity greatly determines the fraction of oscillating cells among a population of isogenic cells. Intrinsic noise-fluctuation in biochemical reactions-has little impact on p53 vari

SUBMITTER: Wang DG 

PROVIDER: S-EPMC6458166 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature