The BEG (PP2A-B55/ENSA/Greatwall) pathway ensures cytokinesis follows chromosome separation

Mol Cell. 2013 Nov 7;52(3):393-405. doi: 10.1016/j.molcel.2013.09.005. Epub 2013 Oct 10.


Cytokinesis follows separase activation and chromosome segregation. This order is ensured in budding yeast by the mitotic exit network (MEN), where Cdc14p dephosphorylates key conserved Cdk1-substrates exemplified by the anaphase spindle-elongation protein Ase1p. However, in metazoans, MEN and Cdc14 function is not conserved. Instead, the PP2A-B55α/ENSA/Greatwall (BEG) pathway controls the human Ase1p ortholog PRC1. In this pathway, PP2A-B55 inhibition is coupled to Cdk1-cyclin B activity, whereas separase inhibition is maintained by cyclin B concentration. This creates two cyclin B thresholds during mitotic exit. Simulation and experiments using PRC1 as a model substrate show that the first threshold permits separase activation and chromosome segregation, and the second permits PP2A-B55 activation and initiation of cytokinesis. Removal of the ENSA/Greatwall (EG) timer module eliminates this second threshold, as well as associated delay in PRC1 dephosphorylation and initiation of cytokinesis, by uncoupling PP2A-B55 from Cdk1-cyclin B activity. Therefore, temporal order during mitotic exit is promoted by the metazoan BEG pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CDC2 Protein Kinase / metabolism
  • Chromosome Segregation / genetics*
  • Chromosomes / genetics
  • Cyclin B / metabolism
  • Cytokinesis / genetics*
  • HeLa Cells
  • Humans
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Mitosis / genetics
  • Phosphoric Monoester Hydrolases / metabolism
  • Protein Phosphatase 2 / genetics
  • Protein Phosphatase 2 / metabolism*
  • Protein Tyrosine Phosphatases
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Separase / genetics
  • Separase / metabolism
  • Signal Transduction / genetics


  • Cyclin B
  • Microtubule-Associated Proteins
  • PPP2R2A protein, human
  • MASTL protein, human
  • Protein-Serine-Threonine Kinases
  • CDC2 Protein Kinase
  • PPP2CA protein, human
  • Protein Phosphatase 2
  • Phosphoric Monoester Hydrolases
  • CDC14A protein, human
  • Protein Tyrosine Phosphatases
  • Separase