A map of protein dynamics during cell-cycle progression and cell-cycle exit

The cell-cycle field has identified the core regulators that drive the cell cycle, but we do not have a clear map of the dynamics of these regulators during cell-cycle progression versus cell-cycle exit. Here we use single-cell time-lapse microscopy of Cyclin-Dependent Kinase 2 (CDK2) activity follo...

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Veröffentlicht in:PLoS biology 2017-09, Vol.15 (9), p.e2003268-e2003268
Hauptverfasser: Gookin, Sara, Min, Mingwei, Phadke, Harsha, Chung, Mingyu, Moser, Justin, Miller, Iain, Carter, Dylan, Spencer, Sabrina L
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container_issue 9
container_start_page e2003268
container_title PLoS biology
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creator Gookin, Sara
Min, Mingwei
Phadke, Harsha
Chung, Mingyu
Moser, Justin
Miller, Iain
Carter, Dylan
Spencer, Sabrina L
description The cell-cycle field has identified the core regulators that drive the cell cycle, but we do not have a clear map of the dynamics of these regulators during cell-cycle progression versus cell-cycle exit. Here we use single-cell time-lapse microscopy of Cyclin-Dependent Kinase 2 (CDK2) activity followed by endpoint immunofluorescence and computational cell synchronization to determine the temporal dynamics of key cell-cycle proteins in asynchronously cycling human cells. We identify several unexpected patterns for core cell-cycle proteins in actively proliferating (CDK2-increasing) versus spontaneously quiescent (CDK2-low) cells, including Cyclin D1, the levels of which we find to be higher in spontaneously quiescent versus proliferating cells. We also identify proteins with concentrations that steadily increase or decrease the longer cells are in quiescence, suggesting the existence of a continuum of quiescence depths. Our single-cell measurements thus provide a rich resource for the field by characterizing protein dynamics during proliferation versus quiescence.
doi_str_mv 10.1371/journal.pbio.2003268
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Here we use single-cell time-lapse microscopy of Cyclin-Dependent Kinase 2 (CDK2) activity followed by endpoint immunofluorescence and computational cell synchronization to determine the temporal dynamics of key cell-cycle proteins in asynchronously cycling human cells. We identify several unexpected patterns for core cell-cycle proteins in actively proliferating (CDK2-increasing) versus spontaneously quiescent (CDK2-low) cells, including Cyclin D1, the levels of which we find to be higher in spontaneously quiescent versus proliferating cells. We also identify proteins with concentrations that steadily increase or decrease the longer cells are in quiescence, suggesting the existence of a continuum of quiescence depths. 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subjects Biochemistry
Biology
Biology and Life Sciences
Cancer
Cell Cycle
Cell Line
Chemistry
Computer applications
Contact Inhibition
Cyclin D1
Cyclin D1 - metabolism
Cyclin-dependent kinase 2
Cyclin-Dependent Kinase 2 - metabolism
Cyclin-dependent kinases
Data collection
Dynamics
Genomes
Humans
Immunofluorescence
Kinases
Medical research
Methods and Resources
Microscopy
Observations
Protein-protein interactions
Proteins
Regulators
Research and Analysis Methods
Single-Cell Analysis
Software
Stem cells
Synchronism
Synchronization
title A map of protein dynamics during cell-cycle progression and cell-cycle exit
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