Polo-like kinase 1 triggers the initiation of cytokinesis in human cells by promoting recruitment of the RhoGEF Ect2 to the central spindle

Dev Cell. 2007 May;12(5):713-25. doi: 10.1016/j.devcel.2007.03.013.

Abstract

Cytokinesis of animal cells requires ingression of the actomyosin-based contractile ring between segregated sister genomes. Localization of the RhoGEF Ect2 to the central spindle at anaphase promotes local activation of the RhoA GTPase, which induces assembly and ingression of the contractile ring. Here we have used BI 2536, an inhibitor of the mitotic kinase Plk1, to analyze the functions of this enzyme during late mitosis in human cells. We show that Plk1 acts after Cdk1 inactivation and independently from Aurora B to promote RhoA accumulation at the equator, contractile ring formation, and cleavage furrow ingression. Inhibition of Plk1 abolishes the interaction of Ect2 with its activator and midzone anchor, HsCyk-4, thereby preventing localization of Ect2 to the central spindle. We propose that late mitotic Plk1 activity promotes recruitment of Ect2 to the central spindle, triggering the initiation of cytokinesis and contributing to cleavage plane specification in human cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinase B
  • Aurora Kinases
  • CDC2 Protein Kinase / metabolism
  • Catalysis / drug effects
  • Cell Cycle Proteins / antagonists & inhibitors
  • Cell Cycle Proteins / metabolism*
  • Chromosomes, Human / genetics
  • Cytokinesis* / drug effects
  • Enzyme Activation / drug effects
  • Guanine Nucleotide Exchange Factors / metabolism*
  • HeLa Cells
  • Humans
  • Microtubule-Associated Proteins / metabolism
  • Models, Biological
  • Protein Binding / drug effects
  • Protein Transport / drug effects
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / metabolism*
  • Pteridines / pharmacology
  • Rho Guanine Nucleotide Exchange Factors
  • Spindle Apparatus / drug effects
  • Spindle Apparatus / metabolism*
  • rhoA GTP-Binding Protein / metabolism

Substances

  • BI 2536
  • Cell Cycle Proteins
  • ECT2 protein, human
  • Guanine Nucleotide Exchange Factors
  • Microtubule-Associated Proteins
  • Proto-Oncogene Proteins
  • Pteridines
  • Rho Guanine Nucleotide Exchange Factors
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1
  • CDC2 Protein Kinase
  • rhoA GTP-Binding Protein