title: The overlooked greatwall: a new perspective on mitotic control.
abstract: The role of the dual specificity protein phosphatase, Cdc25, in activating the cyclin-dependent kinase-cyclin B complex (Cdk1-CycB) by overcoming the inhibitory Wee1 kinase is a long-established principle for mitotic entry. Recently, however, evidence has emerged of a regulatory network that facilitates Cdk1-CycB activity by inhibiting the form of protein phosphatase 2A having a B55 regulatory subunit (PP2A-B55). Here, I review the genetic and biochemical evidence for Greatwall kinase and its substrate Endosulphine as the key components of this previously obscure regulatory network. Not only is the inhibition of PP2A-B55 by phospho-endosulphine required to prevent dephosphorylation of Cdk1-CycB substrates until mitotic exit, but it is also required to promote Cdc25 activity and inhibit Wee1 at mitotic entry. I discuss how these alternating states of preferential PP2A-B55 or Cdk1-CycB activity can have an impact upon the regulation of Polo kinase and its ability to bind different partner proteins as mitosis progresses.
authors: Department of Genetics, University of Cambridge, Downing Street, Cambridge CB3 9JW, UK. dmg25@cam.ac.uk
authors: David M
authors: DM
authors: Glover
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D019926:Cyclin B / Q000378:metabolism; D004330:Drosophila / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D017344:Genes, Insect; D008297:Male; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D010455:Peptides / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D019926:Cyclin B; D029721:Drosophila Proteins; D010455:Peptides; C483180:endos protein, Drosophila; C072004:polo protein, Drosophila; C490167:Gwl protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D054648:Protein Phosphatase 2