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

Ryan L. Hanson, Eric Batchelor

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere11401
JournalMolecular Systems Biology
Volume18
Issue number12
DOIs
StatePublished - Dec 2022

Bibliographical note

Funding Information:
We would like to thank S. Regot who provided the plasmids for the kinase translocation reporters used in this study. We also thank the members of the Batchelor lab, D. Levens, members of the Levens lab, A. Paek, and members of the Paek lab for providing helpful feedback. We thank the University of Minnesota Genomics Core for performing the RNA‐Seq and the University of Minnesota Flow Cytometry Core for providing the instrumentation for the cell cycle analysis and cell death assays. Funding for this work was provided by the University of Minnesota (to EB).

Publisher Copyright:
©2022 The Authors. Published under the terms of the CC BY 4.0 license.

Keywords

  • MAPKs
  • cell stress responses
  • dynamics
  • p53
  • single cells

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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