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

PLoS Biol. 2017 Sep 11;15(9):e2003268. doi: 10.1371/journal.pbio.2003268. eCollection 2017 Sep.

Abstract

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.

MeSH terms

  • Cell Cycle*
  • Cell Line
  • Contact Inhibition
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase 2 / metabolism*
  • Humans
  • Single-Cell Analysis

Substances

  • Cyclin D1
  • Cyclin-Dependent Kinase 2