title: On the regulation of protein phosphatase 2A and its role in controlling entry into and exit from mitosis.
abstract: The process of mitosis involves a comprehensive reorganization of the cell: chromosomes condense, the nuclear envelope breaks down, the mitotic spindle is assembled, cells round up and release their ties to the substrate and so on and so forth. This reorganization is triggered by the activation of the protein kinase, Cyclin-Dependent Kinase 1 (CDK1). The end of mitosis is marked by the proteolysis of the cyclin subunit of CDK1, which terminates kinase activity. At this point, the phosphate moieties that altered the properties of hundreds of proteins to bring about the cellular reorganization are removed by protein phosphatases. At least one protein phosphatase, PP2A-B55, is completely shut off in mitosis. Depletion of this particular form of PP2A accelerates entry into mitosis, and blocks exit from mitosis. Control of this phosphatase is achieved by an inhibitor protein (α-endosulfine or ARPP-19) that becomes inhibitory when phosphorylated by a protein kinase called Greatwall, which is itself a substrate of CDK1. Failure to inhibit PP2A-B55 causes arrest of the cell cycle in G2 phase. I will discuss the role of this control mechanism in the control of mitosis.
authors.affiliation: Clare Hall Laboratories, Cancer Research UK, South Mimms, Herts EN6 3LD, UK. tim.hunt@cancer.org.uk
authors.forename: Tim
authors.initials: T
authors.lastname: Hunt
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D004330:Drosophila; D029721:Drosophila Proteins / Q000502:physiology; D004789:Enzyme Activation; D007399:Interphase / Q000502:physiology; D008938:Mitosis / Q000502:physiology*; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D014981:Xenopus
chemical_list: D029721:Drosophila Proteins; C490167:Gwl protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D054648:Protein Phosphatase 2