title: Phosphorylation relieves autoinhibition of the kinetochore motor Cenp-E.
abstract: 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.
authors.affiliation: Universités Montpellier 2 et 1, IFR122, CRBM, 34293 Montpellier, France; CNRS, UMR 5237, 1919 Route de Mende, 34293 Montpellier, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Espeut
authors.forename: Amaury
authors.initials: A
authors.lastname: Gaussen
authors.forename: Peter
authors.initials: P
authors.lastname: Bieling
authors.forename: Violeta
authors.initials: V
authors.lastname: Morin
authors.forename: Susana
authors.initials: S
authors.lastname: Prieto
authors.forename: Didier
authors.initials: D
authors.lastname: Fesquet
authors.forename: Thomas
authors.initials: T
authors.lastname: Surrey
authors.forename: Ariane
authors.initials: A
authors.lastname: Abrieu
mesh_terms: D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018386:Kinetochores / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D020409:Molecular Motor Proteins; D029867:Xenopus Proteins; C068688:centromere protein E