P53 pulse modulation differentially regulates target gene promoters to regulate cell fate decisions.

ABSTRACT: The p53 tumor suppressor regulates distinct responses to cellular stresses. Although different stresses generate different p53 dynamics, the mechanisms by which cells decode p53 dynamics to differentially regulate target genes are not well understood. Here, we determined in individual cells how canonical p53 target gene promoters vary in responsiveness to features of p53 dynamics. Employing a chemical perturbation approach, we independently modulated p53 pulse amplitude, duration, or frequency, and we then monitored p53 levels and target promoter activation in individual cells. We identified distinct signal processing features-thresholding in response to amplitude modulation, a refractory period in response to duration modulation, and dynamic filtering in response to frequency modulation.

SUBMITTER: Harton MD 

PROVIDER: S-EPMC6761572 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature