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Basal dynamics of p53 reveal transcriptionally attenuated pulses in cycling cells

Item Type:Article
Title:Basal dynamics of p53 reveal transcriptionally attenuated pulses in cycling cells
Creators Name:Loewer, A. and Batchelor, E. and Gaglia, G. and Lahav, G.
Abstract:The tumor suppressor p53 is activated by stress and leads to cellular outcomes such as apoptosis and cell-cycle arrest. Its activation must be highly sensitive to ensure that cells react appropriately to damage. However, proliferating cells often encounter transient damage during normal growth, where cell-cycle arrest or apoptosis may be unfavorable. How does the p53 pathway achieve the right balance between high sensitivity and tolerance to intrinsic damage? Using quantitative time-lapse microscopy of individual human cells, we found that proliferating cells show spontaneous pulses of p53, which are triggered by an excitable mechanism during cell-cycle phases associated with intrinsic DNA damage. However, in the absence of sustained damage, posttranslational modifications keep p53 inactive, preventing it from inducing p21 expression and cell-cycle arrest. Our approach of quantifying basal dynamics in individual cells can now be used to study how other pathways in human cells achieve sensitivity in noisy environments.
Keywords:Cell Cycle, Cell Cycle Proteins, Tumor Cell Line, Cyclin-Dependent Kinase Inhibitor p21, DNA Damage, DNA Repair, DNA-Binding Proteins, Post-Translational Protein Processing, Protein-Serine-Threonine Kinases, Signal Transduction, Tumor Suppressor Protein p53, Tumor Suppressor Proteins
Source:Cell
ISSN:0092-8674
Publisher:Cell Press (U.S.A.)
Volume:142
Number:1
Page Range:89-100
Date:9 July 2010
Official Publication:https://doi.org/10.1016/j.cell.2010.05.031
PubMed:View item in PubMed

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