Cyclin B-Cdk1 inhibits protein phosphatase PP2A-B55 via a Greatwall kinase-independent mechanism

• Published in: The Journal of cell biology Vol. 204; no. 6; pp. 881 - 889
• Main Authors: Okumura, Eiichi, Morita, Atsushi, Wakai, Mizuho, Mochida, Satoru, Hara, Masatoshi, Kishimoto, Takeo
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 17.03.2014; The Rockefeller University Press
• Subjects: Animals; Asterina - cytology; Asterina - enzymology; CDC2 Protein Kinase - metabolism; Cells, Cultured; Cellular biology; Chromosome Segregation; Chromosomes; Cyclin B - metabolism; Enzyme Activation; Enzymes; Meiosis; Phosphoproteins - metabolism; Phosphorylation; Protein Phosphatase 2 - metabolism; Protein Processing, Post-Translational; Proteins; Rabbits
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201307160

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.