Stimulus‐dependent dynamics of p53 in single cells

Many biological networks respond to various inputs through a common signaling molecule that triggers distinct cellular outcomes. One potential mechanism for achieving specific input–output relationships is to trigger distinct dynamical patterns in response to different stimuli. Here we focused on th...

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Bibliographic Details
Published in:Molecular systems biology 2011-05, Vol.7 (1), p.488-n/a
Main Authors: Batchelor, Eric, Loewer, Alexander, Mock, Caroline, Lahav, Galit
Format: Article
Language:English
Subjects:
Cell Line, Tumor
Cellular stress response
Dependence
Digital divide
DNA Breaks, Double-Stranded - radiation effects
DNA damage
Dynamics
Excitability
feedback
Feedback loops
Feedback, Physiological
Gamma Rays
Humans
Immunoblotting
Kinases
live‐cell imaging
Mathematical models
Metabolic Networks and Pathways
Models, Biological
Molecular chains
p53 Protein
Phosphatidylinositol 3-Kinases - metabolism
Radiation
Signal Transduction
Signaling
Single-Cell Analysis
Stress, Physiological
Tumor suppressor genes
Tumor Suppressor Protein p53 - metabolism
Ultraviolet Rays
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Summary:Many biological networks respond to various inputs through a common signaling molecule that triggers distinct cellular outcomes. One potential mechanism for achieving specific input–output relationships is to trigger distinct dynamical patterns in response to different stimuli. Here we focused on the dynamics of p53, a tumor suppressor activated in response to cellular stress. We quantified the dynamics of p53 in individual cells in response to UV and observed a single pulse that increases in amplitude and duration in proportion to the UV dose. This graded response contrasts with the previously described series of fixed pulses in response to γ‐radiation. We further found that while γ‐triggered p53 pulses are excitable, the p53 response to UV is not excitable and depends on continuous signaling from the input‐sensing kinases. Using mathematical modeling and experiments, we identified feedback loops that contribute to specific features of the stimulus‐dependent dynamics of p53, including excitability and input‐duration dependency. Our study shows that different stresses elicit different temporal profiles of p53, suggesting that modulation of p53 dynamics might be used to achieve specificity in this network.
ISSN:1744-4292
1744-4292
DOI:10.1038/msb.2011.20