Progressive activation of CyclinB1-Cdk1 coordinates entry to mitosis

Dev Cell. 2010 Apr 20;18(4):533-43. doi: 10.1016/j.devcel.2010.02.013.


The CyclinB1-Cdk1 kinase is the catalytic activity at the heart of mitosis-promoting factor (MPF), yet fundamental questions concerning its role in mitosis remained unresolved. It is not known when and how rapidly CyclinB1-Cdk1 is activated in mammalian cells, nor how its activation coordinates the substantial changes in the cell at mitosis. Here, we have developed a FRET biosensor specific for CyclinB1-Cdk1 that enables us to assay its activity with very high temporal precision in living human cells. We show that CyclinB1-Cdk1 is inactive in G2 phase and activated at a set time before nuclear envelope breakdown, thereby initiating the events of prophase. CyclinB1-Cdk1 levels rise to their maximum extent over the course of approximately 30 min, and we demonstrate that different levels of CyclinB1-Cdk1 kinase activity trigger different mitotic events, thus revealing how the remarkable reorganization of the cell is coordinated at mitotic entry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase
  • Biosensing Techniques
  • CDC2 Protein Kinase / metabolism*
  • Cell Cycle
  • Cell Line
  • Cyclin B1 / metabolism*
  • Fluorescence Resonance Energy Transfer
  • G2 Phase
  • Humans
  • Mitosis*
  • Models, Biological
  • Nuclear Envelope / metabolism
  • Time Factors
  • Transfection


  • Cyclin B1
  • CDC2 Protein Kinase