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p53 dynamics control cell fate

Item Type:Article
Title:p53 dynamics control cell fate
Creators Name:Purvis, J.E. and Karhohs, K.W. and Mock, C. and Batchelor, E. and Loewer, A. and Lahav, G.
Abstract:Cells transmit information through molecular signals that often show complex dynamical patterns. The dynamic behavior of the tumor suppressor p53 varies depending on the stimulus; in response to double-strand DNA breaks, it shows a series of repeated pulses. Using a computational model, we identified a sequence of precisely timed drug additions that alter p53 pulses to instead produce a sustained p53 response. This leads to the expression of a different set of downstream genes and also alters cell fate: Cells that experience p53 pulses recover from DNA damage, whereas cells exposed to sustained p53 signaling frequently undergo senescence. Our results show that protein dynamics can be an important part of a signal, directly influencing cellular fate decisions.
Keywords:Apoptosis, Biological Models, Cell Aging, Cell Cycle Checkpoints, Cyclin-Dependent Kinase Inhibitor p21, DNA Repair, Double-Stranded DNA Breaks, Gamma Rays, Imidazoles, Piperazines, Signal Transduction, Single-Cell Analysis, Tumor Cell Line, Transcription Factors, Transcriptional Activation, Tumor Suppressor Protein p53, Tumor Suppressor Proteins
Publisher:American Association for the Advancement of Science
Page Range:1440-1444
Date:15 June 2012
Official Publication:https://doi.org/10.1126/science.1218351
PubMed:View item in PubMed

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