Cdk1 phosphorylation of BubR1 controls spindle checkpoint arrest and Plk1-mediated formation of the 3F3/2 epitope

J Cell Biol. 2007 Nov 19;179(4):611-7. doi: 10.1083/jcb.200708044. Epub 2007 Nov 12.

Abstract

Accurate chromosome segregation is controlled by the spindle checkpoint, which senses kinetochore- microtubule attachments and tension across sister kinetochores. An important step in the tension-signaling pathway involves the phosphorylation of an unknown protein by polo-like kinase 1/Xenopus laevis polo-like kinase 1 (Plx1) on kinetochores lacking tension to generate the 3F3/2 phosphoepitope. We report here that the checkpoint protein BubR1 interacts with Plx1 and that phosphorylation of BubR1 by Plx1 generates the 3F3/2 epitope. Formation of the BubR1 3F3/2 epitope by Plx1 requires a prior phosphorylation of BubR1 on Thr 605 by cyclin-dependant kinase 1 (Cdk1). This priming phosphorylation of BubR1 by Cdk1 is required for checkpoint-mediated mitotic arrest and for recruitment of Plx1 and the checkpoint protein Mad2 to unattached kinetochores. Biochemically, formation of the 3F3/2 phosphoepitope by Cdk1 and Plx1 greatly enhances the kinase activity of BubR1. Thus, Cdk1-mediated phosphorylation of BubR1 controls checkpoint arrest and promotes the formation of the kinetochore 3F3/2 epitope.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CDC2 Protein Kinase / metabolism
  • CDC2 Protein Kinase / physiology*
  • Cell Cycle Proteins / metabolism*
  • Epitopes / biosynthesis*
  • Phosphorylation
  • Polo-Like Kinase 1
  • Protein Kinases / metabolism
  • Protein Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Recombinant Proteins / metabolism
  • Spindle Apparatus / physiology*
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism
  • Xenopus Proteins / physiology*
  • Xenopus laevis

Substances

  • Cell Cycle Proteins
  • Epitopes
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • Xenopus Proteins
  • Protein Kinases
  • BUB1B protein, Xenopus
  • Plk1 protein, Xenopus
  • Protein Serine-Threonine Kinases
  • CDC2 Protein Kinase