Phosphorylation Relieves Autoinhibition of the Kinetochore Motor Cenp-E

Julien Espeut (1) , Amaury Gaussen (1) , Peter Bieling (2) , Violeta Morin (1) , Susana Prieto (1) , Didier Fesquet (1) , Thomas Surrey (2) , Ariane Abrieu (1)

1 CRBM - Centre de recherche en Biologie Cellulaire
2 EMBL - EMBL Cell Biology and Biophysics Unit

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.

Domaines: Biochimie, Biologie Moléculaire

Julien Espeut, Amaury Gaussen, Peter Bieling, Violeta Morin, Susana Prieto, et al.. Phosphorylation Relieves Autoinhibition of the Kinetochore Motor Cenp-E. Molecular Cell, 2008, 29 (5), pp.637-43. ⟨10.1016/j.molcel.2008.01.004⟩. ⟨hal-00265137⟩