Complex formation of Plk1 and INCENP required for metaphase-anaphase transition

Nat Cell Biol. 2006 Feb;8(2):180-7. doi: 10.1038/ncb1350. Epub 2005 Dec 25.

Abstract

Mitotic chromosomal dynamics is regulated by the coordinated activities of many mitotic kinases, such as cyclin-dependent kinase 1 (Cdk1), Aurora-B or Polo-like kinase 1 (Plk1), but the mechanisms of their coordination remain unknown. Here, we report that Cdk1 phosphorylates Thr 59 and Thr 388 on inner centromere protein (INCENP), which regulates the localization and kinase activity of Aurora-B from prophase to metaphase. INCENP depletion disrupts Plk1 localization specifically at the kinetochore. This phenotype is rescued by the exogenous expression of INCENP wild type and INCENP mutated at Thr 59 to Ala (T59A), but not at Thr 388 to Ala (T388A). The replacement of endogenous INCENP with T388A resulted in the delay of progression from metaphase to anaphase. We propose that INCENP phosphorylation by Cdk1 is necessary for the recruitment of Plk1 to the kinetochore, and that the complex formation of Plk1 and Aurora-B on INCENP may play crucial roles in the regulation of chromosomal dynamics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anaphase / physiology*
  • Animals
  • Aurora Kinase B
  • Aurora Kinases
  • CDC2 Protein Kinase / metabolism
  • COS Cells
  • Cell Cycle Proteins / metabolism*
  • Cell Nucleus Division / physiology
  • Centrosome / metabolism
  • Chlorocebus aethiops
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Gene Expression / genetics
  • HeLa Cells
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Kinetochores / metabolism
  • Metaphase / physiology*
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Models, Biological
  • Mutation / genetics
  • Neoplasm Proteins / metabolism
  • Phosphorylation
  • Polo-Like Kinase 1
  • Protein Binding
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Small Interfering / genetics
  • Sequence Homology, Amino Acid
  • Survivin
  • Transfection

Substances

  • BIRC5 protein, human
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • INCENP protein, human
  • Incenp protein, mouse
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • Survivin
  • AURKB protein, human
  • Aurkb protein, mouse
  • Aurora Kinase B
  • Aurora Kinases
  • Protein Serine-Threonine Kinases
  • CDC2 Protein Kinase