ArticleScientific reports2019
Roles of cellular heterogeneity, intrinsic and extrinsic noise in variability of p53 oscillation.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Reconstructing noisy gene regulation dynamics using extrinsic-noise-driven neural stochastic differential equations.PLoS computational biology · 2025Article
- Subtle alteration in transcriptional memory governs the lineage-level cell cycle duration heterogeneities of mammalian cells.iScience · 2025Article
- Breaking reflection symmetry: evolving long dynamical cycles in Boolean systems.New journal of physics · 2024Article
- Inference on autoregulation in gene expression with variance-to-mean ratio.Journal of mathematical biology · 2023Article
- Noise facilitates entrainment of a population of uncoupled limit cycle oscillators.Journal of the Royal Society, Interface · 2023Article
- Network design principle for robust oscillatory behaviors with respect to biological noise.eLife · 2022Article
- Computational methods for characterizing and learning from heterogeneous cell signaling data.Current opinion in systems biology · 2021Article
- Propyl isothiocyanate induces apoptosis in gastric cancer cells by oxidative stress via glutathione depletion.Oncology letters · 2019Article
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4 authors.
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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 variability given large amounts of molecules, whereas extrinsic colored noise with proper strength and correlation time contributes much to oscillatory variability in individual cells. With the three sources of noise combined, our results reproduce the experimental observations, suggesting that the long correlation time of colored noise is essential to p53 variability. Compared with previous studies, the current work reveals both the individual and integrated effects of distinct noise sources on p53 variability. This study provides a framework for exploring the variability in oscillations in cellular signaling pathways.
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