title: Mechanisms regulating phosphatase specificity and the removal of individual phosphorylation sites during mitotic exit.
abstract: Entry into mitosis is driven by the activity of kinases, which phosphorylate over 7000 proteins on multiple sites. For cells to exit mitosis and segregate their genome correctly, these phosphorylations must be removed in a specific temporal order. This raises a critical and important question: how are specific phosphorylation sites on an individual protein removed? Traditionally, the temporal order of dephosphorylation was attributed to decreasing kinase activity. However, recent evidence in human cells has identified unique patterns of dephosphorylation during mammalian mitotic exit that cannot be fully explained by the loss of kinase activity. This suggests that specificity is determined in part by phosphatases. In this review, we explore how the physicochemical properties of an individual phosphosite and its surrounding amino acids can affect interactions with a phosphatase. These positive and negative interactions in turn help determine the specific pattern of dephosphorylation required for correct mitotic exit.
authors.affiliation: The Kinghorn Cancer Center, Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia.
authors.forename: Samuel
authors.initials: S
authors.lastname: Rogers
authors.affiliation: The Kinghorn Cancer Center, Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia.
authors.forename: Rachael
authors.initials: R
authors.lastname: McCloy
authors.affiliation: The Kinghorn Cancer Center, Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia.|St. Vincent's Clinical School, Faculty of Medicine, UNSW, Darlinghurst, NSW, Australia.|Department of Thoracic Medicine, St Vincent's Hospital, Darlinghurst, NSW, 2010, Australia.
authors.forename: D Neil
authors.initials: DN
authors.lastname: Watkins
authors.affiliation: The Kinghorn Cancer Center, Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia.|St. Vincent's Clinical School, Faculty of Medicine, UNSW, Darlinghurst, NSW, Australia.
authors.forename: Andrew
authors.identifier: 0000-0003-4536-9226
authors.initials: A
authors.lastname: Burgess
mesh_terms: D059447:Cell Cycle Checkpoints; D006801:Humans; D008938:Mitosis; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D010744:Phosphoric Monoester Hydrolases
keywords: Cdk1; PP1; PP2A; kinase; mitotic exit; phosphatase; phosphorylation