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Coordination of MAPK and p53 dynamics in the cellular responses to DNA damage and oxidative stress

In response to different cellular stresses, the transcription factor p53 undergoes different dynamics. p53 dynamics, in turn, control cell fate. However, distinct stresses can generate the same p53 dynamics but different cell fate outcomes, suggesting integration of dynamic information from other pa...

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Detalles Bibliográficos
Autores principales: Hanson, Ryan L, Batchelor, Eric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9724178/
https://www.ncbi.nlm.nih.gov/pubmed/36472304
http://dx.doi.org/10.15252/msb.202211401
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author Hanson, Ryan L
Batchelor, Eric
author_facet Hanson, Ryan L
Batchelor, Eric
author_sort Hanson, Ryan L
collection PubMed
description In response to different cellular stresses, the transcription factor p53 undergoes different dynamics. p53 dynamics, in turn, control cell fate. However, distinct stresses can generate the same p53 dynamics but different cell fate outcomes, suggesting integration of dynamic information from other pathways is important for cell fate regulation. To determine how MAPK activities affect p53‐mediated responses to DNA breaks and oxidative stress, we simultaneously tracked p53 and either ERK, JNK, or p38 activities in single cells. While p53 dynamics were comparable between the stresses, cell fate outcomes were distinct. Combining MAPK dynamics with p53 dynamics was important for distinguishing between the stresses and for generating temporal ordering of cell fate pathways. Furthermore, cross‐talk between MAPKs and p53 controlled the balance between proliferation and cell death. These findings provide insight into how cells integrate signaling pathways with distinct temporal patterns of activity to encode stress specificity and drive different cell fate decisions.
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spelling pubmed-97241782022-12-08 Coordination of MAPK and p53 dynamics in the cellular responses to DNA damage and oxidative stress Hanson, Ryan L Batchelor, Eric Mol Syst Biol Articles In response to different cellular stresses, the transcription factor p53 undergoes different dynamics. p53 dynamics, in turn, control cell fate. However, distinct stresses can generate the same p53 dynamics but different cell fate outcomes, suggesting integration of dynamic information from other pathways is important for cell fate regulation. To determine how MAPK activities affect p53‐mediated responses to DNA breaks and oxidative stress, we simultaneously tracked p53 and either ERK, JNK, or p38 activities in single cells. While p53 dynamics were comparable between the stresses, cell fate outcomes were distinct. Combining MAPK dynamics with p53 dynamics was important for distinguishing between the stresses and for generating temporal ordering of cell fate pathways. Furthermore, cross‐talk between MAPKs and p53 controlled the balance between proliferation and cell death. These findings provide insight into how cells integrate signaling pathways with distinct temporal patterns of activity to encode stress specificity and drive different cell fate decisions. John Wiley and Sons Inc. 2022-12-06 /pmc/articles/PMC9724178/ /pubmed/36472304 http://dx.doi.org/10.15252/msb.202211401 Text en ©2022 The Authors. Published under the terms of the CC BY 4.0 license. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Hanson, Ryan L
Batchelor, Eric
Coordination of MAPK and p53 dynamics in the cellular responses to DNA damage and oxidative stress
title Coordination of MAPK and p53 dynamics in the cellular responses to DNA damage and oxidative stress
title_full Coordination of MAPK and p53 dynamics in the cellular responses to DNA damage and oxidative stress
title_fullStr Coordination of MAPK and p53 dynamics in the cellular responses to DNA damage and oxidative stress
title_full_unstemmed Coordination of MAPK and p53 dynamics in the cellular responses to DNA damage and oxidative stress
title_short Coordination of MAPK and p53 dynamics in the cellular responses to DNA damage and oxidative stress
title_sort coordination of mapk and p53 dynamics in the cellular responses to dna damage and oxidative stress
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9724178/
https://www.ncbi.nlm.nih.gov/pubmed/36472304
http://dx.doi.org/10.15252/msb.202211401
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