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. We then showed that the signal processing features not only affect p53 target promoter activation, they also affect p53 regulation and downstream cellular functions. Our study shows how different promoters can differentially decode features of p53 dynamics to generate distinct responses, providing insight into how perturbing p53 dynamics can be used to generate distinct cell fates.

Stochastic fluctuations, termed “noise,” in the level of biological molecules can greatly impact cellular functions. While biological noise can sometimes be detrimental, recent studies have provided an increasing number of examples in which biological noise can be functionally beneficial. Rather than provide an exhaustive review of the growing literature in this field, in this review we focus on single cell studies based on quantitative microscopy that have generated a deeper understanding of the sources, characteristics, limitations, and benefits of biological noise. Specifically, we highlight studies showing how noise can help coordinate the expression of multiple downstream target genes, impact the channel capacity of signaling networks, and interact synergistically with oscillatory dynamics to enhance the sensitivity of signal processing. We conclude with a discussion of current challenges and future opportunities.