Loewer, Alexander ; Batchelor, Eric ; Gaglia, Giorgio ; Lahav, Galit (2010)
Basal dynamics of p53 reveal transcriptionally attenuated pulses in cycling cells.
In: Cell, 142 (1)
Artikel, Bibliographie
Kurzbeschreibung (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.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2010 |
| Autor(en): | Loewer, Alexander ; Batchelor, Eric ; Gaglia, Giorgio ; Lahav, Galit |
| Art des Eintrags: | Bibliographie |
| Titel: | Basal dynamics of p53 reveal transcriptionally attenuated pulses in cycling cells. |
| Sprache: | Englisch |
| Publikationsjahr: | 2010 |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Cell |
| Jahrgang/Volume einer Zeitschrift: | 142 |
| (Heft-)Nummer: | 1 |
| Kurzbeschreibung (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. |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Systems Biology of the Stress Response |
| Hinterlegungsdatum: | 02 Sep 2015 08:52 |
| Letzte Änderung: | 02 Sep 2015 08:52 |
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