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| Item Type: | Article |
|---|---|
| Title: | Basal dynamics of p53 reveal transcriptionally attenuated pulses in cycling cells |
| Creators Name: | Loewer, A., Batchelor, E., 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 |
| 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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