Phosphorylation relieves autoinhibition of the kinetochore motor Cenp-E

Mol Cell. 2008 Mar 14;29(5):637-43. doi: 10.1016/j.molcel.2008.01.004.


During mitosis, chromosome alignment depends on the regulated dynamics of microtubules and on motor protein activities. At the kinetochore, the interplay between microtubule-binding proteins, motors, and kinases is poorly understood. Cenp-E is a kinetochore-associated kinesin involved in chromosome congression, but the mechanism by which this is achieved is unclear. Here, we present a study of the regulation of Cenp-E motility by using purified full-length (FL) Xenopus Cenp-E protein, which demonstrates that FL Cenp-E is a genuine plus-end-directed motor. Furthermore, we find that the Cenp-E tail completely blocks the motility of Cenp-E in vitro. This is achieved through direct interaction between its motor and tail domains. Finally, we show that Cenp-E autoinhibition is reversed by MPS1- or CDK1-cyclin B-mediated phosphorylation of the Cenp-E tail. This suggests a model of dynamic control of Cenp-E motility, and hence chromosome congression, dependent upon phosphorylation at the kinetochore.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Kinetochores / metabolism*
  • Microtubules / metabolism
  • Microtubules / ultrastructure
  • Models, Molecular
  • Molecular Motor Proteins / chemistry
  • Molecular Motor Proteins / genetics
  • Molecular Motor Proteins / metabolism*
  • Phosphorylation
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism*
  • Xenopus laevis


  • Chromosomal Proteins, Non-Histone
  • Molecular Motor Proteins
  • Xenopus Proteins
  • centromere protein E