title: The master Greatwall kinase, a critical regulator of mitosis and meiosis.
abstract: Entry into mitosis requires the coordinated activation of various protein kinases and phosphatases that together activate sequential signaling pathways allowing entry, progression and exit of mitosis. The limiting step is thought to be the activation of the mitotic Cdk1-cyclin B kinase. However, this model has recently evolved with new data showing that in addition to the Cdk1-cyclin B complex, Greatwall (Gwl) kinase is also required to enter into and maintain mitosis. This new concept proposes that entry into mitosis is now based on the combined activation of both kinases Cdk1-cyclin B and Gwl, the former promoting massive phosphorylation of mitotic substrates and the latter inhibiting PP2A-B55 phosphatase responsible for dephosphorylation of these substrates. Activated Gwl phosphorylates both Arpp19 and ENSA, which associate and inhibit PP2A-B55. This pathway seems relatively well conserved from yeast to humans, although some differences appear based on models or techniques used. While Gwl is activated by phosphorylation, its inactivation requires dephosphorylation of critical residues. Several phosphatases such as PP1, PP2A-B55 and FCP1 are required to control the dephosphorylation and inactivation of Gwl and a properly regulated mitotic exit. Gwl has also been reported to be involved in cancer processes and DNA damage recovery. These new findings support the idea that the Gwl-Arpp19/ENSA-PP2A-B55 pathway is essential to achieve an efficient division of cells and to maintain genomic stability.
authors.affiliation: Equipe Labellisée Ligue Contre le Cancer. Université de Montpellier, Centre de Recherche de Biologie Cellulaire de Montpellier, CNRS UMR 5237, France.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Vigneron
authors.forename: Perle
authors.initials: P
authors.lastname: Robert
authors.forename: Khaled
authors.initials: K
authors.lastname: Hached
authors.forename: Lena
authors.initials: L
authors.lastname: Sundermann
authors.forename: Sophie
authors.initials: S
authors.lastname: Charrasse
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Labbé
authors.forename: Anna
authors.initials: A
authors.lastname: Castro
authors.forename: Thierry
authors.initials: T
authors.lastname: Lorca
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D008540:Meiosis / Q000502:physiology*; D008938:Mitosis / Q000502:physiology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D019926:Cyclin B; D029867:Xenopus Proteins; C544010:MASTL protein, Xenopus; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase