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Science 330 (6011): 1670-1673

Copyright © 2010 by the American Association for the Advancement of Science

Greatwall Phosphorylates an Inhibitor of Protein Phosphatase 2A That Is Essential for Mitosis

Satoru Mochida,1,2 Sarah L. Maslen,1 Mark Skehel,1 Tim Hunt1,*

Abstract: Entry into mitosis in eukaryotes requires the activity of cyclin-dependent kinase 1 (Cdk1). Cdk1 is opposed by protein phosphatases in two ways: They inhibit activation of Cdk1 by dephosphorylating the protein kinases Wee1 and Myt1 and the protein phosphatase Cdc25 (key regulators of Cdk1), and they also antagonize Cdk1’s own phosphorylation of downstream targets. A particular form of protein phosphatase 2A (PP2A) containing a B55{delta} subunit (PP2A- B55{delta}) is the major protein phosphatase that acts on model CDK substrates in Xenopus egg extracts and has antimitotic activity. The activity of PP2A-B55{delta} is high in interphase and low in mitosis, exactly opposite that of Cdk1. We report that inhibition of PP2A-B55{delta} results from a small protein, known as {alpha}-endosulfine (Ensa), that is phosphorylated in mitosis by the protein kinase Greatwall (Gwl). This converts Ensa into a potent and specific inhibitor of PP2A-B55{delta}. This pathway represents a previously unknown element in the control of mitosis.

1 Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK.
2 Priority Organization for Innovation and Excellence, Kumamoto University, 2-2-1 Honjo, Kumamoto, Kumamoto 860-0811, Japan.

* To whom correspondence should be addressed. E-mail: tim.hunt{at}cancer.org.uk


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