Choice of Plk1 docking partners during mitosis and cytokinesis is controlled by the activation state of Cdk1

Nat Cell Biol. 2007 Apr;9(4):436-44. doi: 10.1038/ncb1557. Epub 2007 Mar 11.

Abstract

Spatial and temporal coordination of polo-like kinase 1 (Plk1) activity is necessary for mitosis and cytokinesis, and this is achieved through binding to phosphorylated docking proteins with distinct subcellular localizations. Although cyclin-dependent kinase 1 (Cdk1) creates these phosphorylated docking sites in metaphase, a general principle that explains how Plk1 activity is controlled in anaphase after Cdk1 inactivation is lacking. Here, we show that the microtubule-associated protein regulating cytokinesis (PRC1) is an anaphase-specific binding partner for Plk1, and that this interaction is required for cytokinesis. In anaphase, Plk1 creates its own docking site on PRC1, whereas in metaphase Cdk1 phosphorylates PRC1 adjacent to this docking site and thereby prevents binding of Plk1. Mutation of these Cdk1-sites results in a form of PRC1 that prematurely recruits Plk1 to the spindle during prometaphase and blocks mitotic progression. The activation state of Cdk1, therefore, controls the switch of Plk1 localization from centrosomes and kinetochores during metaphase, to the central spindle during anaphase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CDC2 Protein Kinase / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Division / physiology
  • Centrosome / metabolism
  • Cytokinesis / physiology*
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme Activation
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • HeLa Cells
  • Humans
  • Immunoprecipitation
  • Kinetochores / metabolism
  • Microscopy, Fluorescence
  • Microtubules / metabolism
  • Mitosis / physiology*
  • Models, Biological
  • Molecular Sequence Data
  • Phosphorylation
  • Polo-Like Kinase 1
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Small Interfering / genetics
  • Sequence Homology, Amino Acid
  • Spindle Apparatus / metabolism

Substances

  • Cell Cycle Proteins
  • PRC1 protein, human
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • Green Fluorescent Proteins
  • Protein Serine-Threonine Kinases
  • CDC2 Protein Kinase