Aurora kinases and protein phosphatase 1 mediate chromosome congression through regulation of CENP-E

Cell. 2010 Aug 6;142(3):444-55. doi: 10.1016/j.cell.2010.06.039.

Abstract

Opposing roles of Aurora kinases and protein phosphatase 1 (PP1) during mitosis have long been suggested. Here, we demonstrate that Aurora kinases A and B phosphorylate a conserved residue on the kinetochore motor CENP-E. PP1 binds CENP-E via a motif overlapping this phosphorylation site and binding is disrupted by Aurora phosphorylation. Phosphorylation of CENP-E by the Auroras is enriched at spindle poles, disrupting binding of PP1 and reducing CENP-E's affinity for individual microtubules. This phosphorylation is required for CENP-E-mediated towing of initially polar chromosomes toward the cell center. Kinetochores on such chromosomes cannot make subsequent stable attachment to spindle microtubules when dephosphorylation of CENP-E or rebinding of PP1 to CENP-E is blocked. Thus, an Aurora/PP1 phosphorylation switch modulates CENP-E motor activity as an essential feature of chromosome congression from poles and localized PP1 delivery by CENP-E to the outer kinetochore is necessary for stable microtubule capture by those chromosomes.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aurora Kinases
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosomes / metabolism*
  • HeLa Cells
  • Humans
  • Kinetochores / metabolism
  • Microtubules / metabolism
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Phosphatase 1 / metabolism*
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / metabolism*
  • Sequence Alignment
  • Spindle Apparatus / metabolism
  • Xenopus laevis / metabolism*

Substances

  • Chromosomal Proteins, Non-Histone
  • centromere protein E
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • Protein Phosphatase 1