Greatwall maintains mitosis through regulation of PP2A.
Greatwall (GW) is a new kinase that has an important function in the activation and the maintenance of cyclin B-Cdc2 activity. Although the mechanism by which it induces this effect is unknown, it has been suggested that GW could maintain cyclin B-Cdc2 activity by regulating its activation loop. Using Xenopus egg extracts, we show that GW depletion promotes mitotic exit, even in the presence of a high cyclin B-Cdc2 activity by inducing dephosphorylation of mitotic substrates. These results indicate that GW does not maintain the mitotic state by regulating the cyclin B-Cdc2 activation loop but by regulating a phosphatase. This phosphatase is PP2A; we show that (1) PP2A binds GW, (2) the inhibition or the specific depletion of this phosphatase from mitotic extracts rescues the phenotype induced by GW inactivation and (3) the PP2A-dependent dephosphorylation of cyclin B-Cdc2 substrates is increased in GW-depleted Xenopus egg extracts. These results suggest that mitotic entry and maintenance is not only mediated by the activation of cyclin B-Cdc2 but also by the regulation of PP2A by GW.
Vigneron
Suzanne
S
Centre de Recherche de Biochimie Macromoléculaire, CNRS UMR 5237, IFR 122, Labellisée Ligue Nationale Contre le Cancer, Universités Montpellier 2 et 1, Montpellier, France.
Brioudes
Estelle
E
Burgess
Andrew
A
Labbé
Jean-Claude
JC
Lorca
Thierry
T
Castro
Anna
A
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D052998:Microcystins / Q000378:metabolism; D008938:Mitosis; D008954:Models, Biological; D019319:Okadaic Acid / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000502:physiology*; D013094:Spermatozoa / Q000378:metabolism; D029867:Xenopus Proteins / Q000737:chemistry / Q000502:physiology*; D014982:Xenopus laevis / Q000378:metabolism*
D052998:Microcystins; D029867:Xenopus Proteins; D019319:Okadaic Acid; C078588:microcystin; C544010:MASTL protein, Xenopus; D017346:Protein Serine-Threonine Kinases; D054648:Protein Phosphatase 2
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