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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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Detalles Bibliográficos
Autores principales: Batchelor, Eric, Loewer, Alexander, Mock, Caroline, Lahav, Galit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3130553/
https://www.ncbi.nlm.nih.gov/pubmed/21556066
http://dx.doi.org/10.1038/msb.2011.20
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author Batchelor, Eric
Loewer, Alexander
Mock, Caroline
Lahav, Galit
author_facet Batchelor, Eric
Loewer, Alexander
Mock, Caroline
Lahav, Galit
author_sort Batchelor, Eric
collection PubMed
description 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.
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spelling pubmed-31305532011-07-06 Stimulus-dependent dynamics of p53 in single cells Batchelor, Eric Loewer, Alexander Mock, Caroline Lahav, Galit Mol Syst Biol Report 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. Nature Publishing Group 2011-05-10 /pmc/articles/PMC3130553/ /pubmed/21556066 http://dx.doi.org/10.1038/msb.2011.20 Text en Copyright © 2011, EMBO and Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial Share Alike 3.0 Unported License, which allows readers to alter, transform, or build upon the article and then distribute the resulting work under the same or similar license to this one. The work must be attributed back to the original author and commercial use is not permitted without specific permission.
spellingShingle Report
Batchelor, Eric
Loewer, Alexander
Mock, Caroline
Lahav, Galit
Stimulus-dependent dynamics of p53 in single cells
title Stimulus-dependent dynamics of p53 in single cells
title_full Stimulus-dependent dynamics of p53 in single cells
title_fullStr Stimulus-dependent dynamics of p53 in single cells
title_full_unstemmed Stimulus-dependent dynamics of p53 in single cells
title_short Stimulus-dependent dynamics of p53 in single cells
title_sort stimulus-dependent dynamics of p53 in single cells
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3130553/
https://www.ncbi.nlm.nih.gov/pubmed/21556066
http://dx.doi.org/10.1038/msb.2011.20
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