Phosphorylation at serine 331 is required for Aurora B activation

J Cell Biol. 2011 Oct 31;195(3):449-66. doi: 10.1083/jcb.201104023. Epub 2011 Oct 24.

Abstract

Aurora B kinase activity is required for successful cell division. In this paper, we show that Aurora B is phosphorylated at serine 331 (Ser331) during mitosis and that phosphorylated Aurora B localizes to kinetochores in prometaphase cells. Chk1 kinase is essential for Ser331 phosphorylation during unperturbed prometaphase or during spindle disruption by taxol but not nocodazole. Phosphorylation at Ser331 is required for optimal phosphorylation of INCENP at TSS residues, for Survivin association with the chromosomal passenger complex, and for complete Aurora B activation, but it is dispensable for Aurora B localization to centromeres, for autophosphorylation at threonine 232, and for association with INCENP. Overexpression of Aurora B(S331A), in which Ser331 is mutated to alanine, results in spontaneous chromosome missegregation, cell multinucleation, unstable binding of BubR1 to kinetochores, and impaired mitotic delay in the presence of taxol. We propose that Chk1 phosphorylates Aurora B at Ser331 to fully induce Aurora B kinase activity. These results indicate that phosphorylation at Ser331 is an essential mechanism for Aurora B activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aurora Kinase B
  • Aurora Kinases
  • CHO Cells
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosome Segregation
  • Cricetinae
  • Enzyme Activation
  • Humans
  • Kinetochores / metabolism
  • Microscopy, Fluorescence
  • Mitosis
  • Molecular Sequence Data
  • Paclitaxel / pharmacology
  • Phosphorylation
  • Protein Binding
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Serine / genetics*
  • Serine / metabolism

Substances

  • Chromosomal Proteins, Non-Histone
  • INCENP protein, human
  • Serine
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • Paclitaxel

Associated data

  • PDB/2BFY