title: Cyclin B-Cdk1 inhibits protein phosphatase PP2A-B55 via a Greatwall kinase-independent mechanism.
abstract: Entry into M phase is governed by cyclin B-Cdk1, which undergoes both an initial activation and subsequent autoregulatory activation. A key part of the autoregulatory activation is the cyclin B-Cdk1-dependent inhibition of the protein phosphatase 2A (PP2A)-B55, which antagonizes cyclin B-Cdk1. Greatwall kinase (Gwl) is believed to be essential for the autoregulatory activation because Gwl is activated downstream of cyclin B-Cdk1 to phosphorylate and activate α-endosulfine (Ensa)/Arpp19, an inhibitor of PP2A-B55. However, cyclin B-Cdk1 becomes fully activated in some conditions lacking Gwl, yet how this is accomplished remains unclear. We show here that cyclin B-Cdk1 can directly phosphorylate Arpp19 on a different conserved site, resulting in inhibition of PP2A-B55. Importantly, this novel bypass is sufficient for cyclin B-Cdk1 autoregulatory activation. Gwl-dependent phosphorylation of Arpp19 is nonetheless necessary for downstream mitotic progression because chromosomes fail to segregate properly in the absence of Gwl. Such a biphasic regulation of Arpp19 results in different levels of PP2A-B55 inhibition and hence might govern its different cellular roles.
authors.affiliation: Laboratory of Cell and Developmental Biology, Graduate School of Bioscience, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Okumura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Morita
authors.forename: Mizuho
authors.initials: M
authors.lastname: Wakai
authors.forename: Satoru
authors.initials: S
authors.lastname: Mochida
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Hara
authors.forename: Takeo
authors.initials: T
authors.lastname: Kishimoto
mesh_terms: D000818:Animals; D047288:Asterina / Q000166:cytology / Q000201:enzymology*; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002478:Cells, Cultured; D020090:Chromosome Segregation; D019926:Cyclin B / Q000378:metabolism*; D004789:Enzyme Activation; D008540:Meiosis; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011817:Rabbits
chemical_list: D019926:Cyclin B; D010750:Phosphoproteins; C064321:cyclic AMP-regulated phosphoprotein 19; D016203:CDC2 Protein Kinase; D054648:Protein Phosphatase 2