Mönke, Gregor ; Cristiano, Elena ; Finzel, Ana ; Friedrich, Dhana ; Herzel, Hanspeter ; Falcke, Martin ; Loewer, Alexander (2017)
Excitability in the p53 network mediates robust signaling with tunable activation thresholds in single cells.
In: Scientific Reports, 2017, 7
doi: 10.1038/srep46571
Artikel, Zweitveröffentlichung, Verlagsversion
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Kurzbeschreibung (Abstract)
Cellular signaling systems precisely transmit information in the presence of molecular noise while retaining flexibility to accommodate the needs of individual cells. To understand design principles underlying such versatile signaling, we analyzed the response of the tumor suppressor p53 to varying levels of DNA damage in hundreds of individual cells and observed a switch between distinct signaling modes characterized by isolated pulses and sustained oscillations of p53 accumulation. Guided by dynamic systems theory we show that this requires an excitable network structure comprising positive feedback and provide experimental evidence for its molecular identity. The resulting data-driven model reproduced all features of measured signaling responses and is sufficient to explain their heterogeneity in individual cells. We present evidence that heterogeneity in the levels of the feedback regulator Wip1 sets cell-specific thresholds for p53 activation, providing means to modulate its response through interacting signaling pathways. Our results demonstrate how excitable signaling networks can provide high specificity, sensitivity and robustness while retaining unique possibilities to adjust their function to the physiology of individual cells.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2017 |
| Autor(en): | Mönke, Gregor ; Cristiano, Elena ; Finzel, Ana ; Friedrich, Dhana ; Herzel, Hanspeter ; Falcke, Martin ; Loewer, Alexander |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | Excitability in the p53 network mediates robust signaling with tunable activation thresholds in single cells |
| Sprache: | Deutsch |
| Publikationsjahr: | 2017 |
| Publikationsdatum der Erstveröffentlichung: | 2017 |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Scientific Reports |
| Jahrgang/Volume einer Zeitschrift: | 7 |
| DOI: | 10.1038/srep46571 |
| URL / URN: | https://doi.org/10.1038/srep46571 |
| Herkunft: | Zweitveröffentlichung aus gefördertem Golden Open Access |
| Kurzbeschreibung (Abstract): | Cellular signaling systems precisely transmit information in the presence of molecular noise while retaining flexibility to accommodate the needs of individual cells. To understand design principles underlying such versatile signaling, we analyzed the response of the tumor suppressor p53 to varying levels of DNA damage in hundreds of individual cells and observed a switch between distinct signaling modes characterized by isolated pulses and sustained oscillations of p53 accumulation. Guided by dynamic systems theory we show that this requires an excitable network structure comprising positive feedback and provide experimental evidence for its molecular identity. The resulting data-driven model reproduced all features of measured signaling responses and is sufficient to explain their heterogeneity in individual cells. We present evidence that heterogeneity in the levels of the feedback regulator Wip1 sets cell-specific thresholds for p53 activation, providing means to modulate its response through interacting signaling pathways. Our results demonstrate how excitable signaling networks can provide high specificity, sensitivity and robustness while retaining unique possibilities to adjust their function to the physiology of individual cells. |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-68921 |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Systems Biology of the Stress Response |
| Hinterlegungsdatum: | 22 Okt 2017 19:55 |
| Letzte Änderung: | 02 Aug 2024 12:33 |
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| Suche nach Titel in: | TUfind oder in Google |
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- Excitability in the p53 network mediates robust signaling with tunable activation thresholds in single cells. (deposited 22 Okt 2017 19:55) [Gegenwärtig angezeigt]
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