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MBC in Press, published online ahead of print October 6, 2004
Mol. Biol. Cell 10.1091/mbc.E04-07-0598

A more recent version of this article appeared on December 1, 2004
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Submitted on July 16, 2004
Revised on September 1, 2004
Accepted on September 29, 2004

Plk1 Regulates Activation of the Anaphase Promoting Complex by Phosphorylating and Triggering SCF{beta}TrCP-dependent Destruction of the APC Inhibitor Emi1

David V. Hansen, Alexander V. Loktev, Kenneth H. Ban, and Peter K. Jackson*

Department of Pathology, Stanford University School of Medicine, Palo Alto, CA 94305

Monitoring Editor: Tim Stearns

Progression through mitosis requires activation of cyclin B/Cdk1 and its downstream targets, including polo-like kinase and the anaphase promoting complex (APC), the ubiquitin ligase directing degradation of cyclins A and B. Recent evidence shows that APC activation requires destruction of the APC inhibitor, Emi1. In prophase, phosphorylation of Emi1 generates a D-pS-G-X-X-pS degron to recruit the SCF{beta}TrCP ubiquitin ligase, causing Emi1 destruction and allowing progression beyond prometaphase, but the kinases directing this phosphorylation remain undefined. We show here that the polo-like kinase Plk1 is strictly required for Emi1 destruction and that overexpression of Plk1 is sufficient to trigger Emi1 destruction. Plk1 stimulates Emi1 phosphorylation, {beta}TrCP binding, and ubiquitination in vitro and cyclin B/Cdk1 enhances these effects. Plk1 binds to Emi1 in mitosis and the two proteins colocalize on the mitotic spindle poles, suggesting that Plk1 may spatially control Emi1 destruction. These data support the hypothesis that Plk1 activates the APC by directing the SCF-dependent destruction of Emi1 in prophase.

*Corresponding author. E-mail: pjackson{at}stanford.edu






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