CDK-dependent potentiation of MPS1 kinase activity is essential to the mitotic checkpoint. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Current Biology - CB Année : 2012

CDK-dependent potentiation of MPS1 kinase activity is essential to the mitotic checkpoint.

Résumé

Accurate chromosome segregation relies upon a mitotic checkpoint that monitors kinetochore attachment toward opposite spindle poles before enabling chromosome disjunction [1]. The MPS1/TTK protein kinase is a core component of the mitotic checkpoint that lies upstream of MAD2 and BubR1 both at the kinetochore and in the cytoplasm [2, 3]. To gain insight into the mechanisms underlying the regulation of MPS1 kinase, we undertook the identification of Xenopus MPS1 phosphorylation sites by mass spectrometry. We mapped several phosphorylation sites onto MPS1 and we show that phosphorylation of S283 in the noncatalytic region of MPS1 is required for full kinase activity. This phosphorylation potentiates MPS1 catalytic efficiency without impairing its affinity for the substrates. By using Xenopus egg extracts depleted of endogenous MPS1 and reconstituted with single point mutants, we show that phosphorylation of S283 is essential to activate the mitotic checkpoint. This phosphorylation does not regulate the localization of MPS1 to the kinetochore but is required for the recruitment of MAD1/MAD2, demonstrating its role at the kinetochore. Constitutive phosphorylation of S283 lowers the number of kinetochores required to hold the checkpoint, which suggests that CDK-dependent phosphorylation of MPS1 is essential to sustain the mitotic checkpoint when few kinetochores remain unattached.
Fichier principal
Vignette du fichier
CDK-dependent potentiation of MPS1 Current Biol 2012.pdf (1.46 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-00715231 , version 1 (14-10-2022)

Identifiants

Citer

Violeta Morin, Susana Prieto, Sabrina Melines, Sonia Hem, Michel Rossignol, et al.. CDK-dependent potentiation of MPS1 kinase activity is essential to the mitotic checkpoint.. Current Biology - CB, 2012, 22 (4), pp.289-95. ⟨10.1016/j.cub.2011.12.048⟩. ⟨hal-00715231⟩
132 Consultations
15 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More