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Disentangling Pro-mitotic Signaling during Cell Cycle Progression using Time-Resolved Single-Cell Imaging.

Benary, Manuela ; Bohn, Stefan ; Lüthen, Mareen ; Nolis, Ilias K. ; Blüthgen, Nils ; Loewer, Alexander (2020)
Disentangling Pro-mitotic Signaling during Cell Cycle Progression using Time-Resolved Single-Cell Imaging.
In: Cell reports, 31 (2)
doi: 10.1016/j.celrep.2020.03.078
Artikel, Bibliographie

Kurzbeschreibung (Abstract)

Cells rely on input from extracellular growth factors to control their proliferation during development and adult homeostasis. Such mitogenic inputs are transmitted through multiple signaling pathways that synergize to precisely regulate cell cycle entry and progression. Although the architecture of these signaling networks has been characterized in molecular detail, their relative contribution, especially at later cell cycle stages, remains largely unexplored. By combining quantitative time-resolved measurements of fluorescent reporters in untransformed human cells with targeted pharmacological inhibitors and statistical analysis, we quantify epidermal growth factor (EGF)-induced signal processing in individual cells over time and dissect the dynamic contribution of downstream pathways. We define signaling features that encode information about extracellular ligand concentrations and critical time windows for inducing cell cycle transitions. We show that both extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K) activity are necessary for initial cell cycle entry, whereas only PI3K affects the duration of S phase at later stages of mitogenic signaling.

Typ des Eintrags: Artikel
Erschienen: 2020
Autor(en): Benary, Manuela ; Bohn, Stefan ; Lüthen, Mareen ; Nolis, Ilias K. ; Blüthgen, Nils ; Loewer, Alexander
Art des Eintrags: Bibliographie
Titel: Disentangling Pro-mitotic Signaling during Cell Cycle Progression using Time-Resolved Single-Cell Imaging.
Sprache: Englisch
Publikationsjahr: 14 April 2020
Titel der Zeitschrift, Zeitung oder Schriftenreihe: Cell reports
Jahrgang/Volume einer Zeitschrift: 31
(Heft-)Nummer: 2
DOI: 10.1016/j.celrep.2020.03.078
Kurzbeschreibung (Abstract):

Cells rely on input from extracellular growth factors to control their proliferation during development and adult homeostasis. Such mitogenic inputs are transmitted through multiple signaling pathways that synergize to precisely regulate cell cycle entry and progression. Although the architecture of these signaling networks has been characterized in molecular detail, their relative contribution, especially at later cell cycle stages, remains largely unexplored. By combining quantitative time-resolved measurements of fluorescent reporters in untransformed human cells with targeted pharmacological inhibitors and statistical analysis, we quantify epidermal growth factor (EGF)-induced signal processing in individual cells over time and dissect the dynamic contribution of downstream pathways. We define signaling features that encode information about extracellular ligand concentrations and critical time windows for inducing cell cycle transitions. We show that both extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K) activity are necessary for initial cell cycle entry, whereas only PI3K affects the duration of S phase at later stages of mitogenic signaling.

ID-Nummer: pmid:32294432
Fachbereich(e)/-gebiet(e): 10 Fachbereich Biologie
10 Fachbereich Biologie > Systems Biology of the Stress Response
Hinterlegungsdatum: 20 Apr 2020 11:32
Letzte Änderung: 20 Apr 2020 11:32
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