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Basal dynamics of p53 reveal transcriptionally attenuated pulses in cycling cells.

Loewer, Alexander ; Batchelor, Eric ; Gaglia, Giorgio ; Lahav, Galit :
Basal dynamics of p53 reveal transcriptionally attenuated pulses in cycling cells.
In: Cell, 142 (1) S. 89-100. ISSN 1097-4172
[Artikel] , (2010)

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
Titel: Basal dynamics of p53 reveal transcriptionally attenuated pulses in cycling cells.
Sprache: Englisch
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.

Titel der Zeitschrift, Zeitung oder Schriftenreihe: Cell
Band: 142
(Heft-)Nummer: 1
Fachbereich(e)/-gebiet(e): 10 Fachbereich Biologie
10 Fachbereich Biologie > Systems Biology of the Stress Response
Hinterlegungsdatum: 02 Sep 2015 08:52
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