APC/C-Cdh1-mediated degradation of the Polo kinase Cdc5 promotes the return of Cdc14 into the nucleolus

Clara Visintin; Brett N. Tomson; Rami Rahal; Jennifer Paulson; Michael Cohen; Jack Taunton; Angelika Amon; Rosella Visintin

doi:10.1101/gad.1601308

APC/C-Cdh1-mediated degradation of the Polo kinase Cdc5 promotes the return of Cdc14 into the nucleolus

¹ Department of Experimental Oncology, European Institute of Oncology, Milano 20141, Italy;
² Center for Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;
³ Department of Cellular and Molecular Pathology, University of California at San Francisco, San Francisco, California 94143, USA

Abstract

In the budding yeast Saccharomyces cerevisiae, the protein phosphatase Cdc14 triggers exit from mitosis by promoting the inactivation of cyclin-dependent kinases (CDKs). Cdc14’s activity is controlled by Cfi1/Net1, which holds and inhibits the phosphatase in the nucleolus from G1 until metaphase. During anaphase, two regulatory networks, the Cdc14 Early Anaphase Release (FEAR) network and the Mitotic Exit Network (MEN), promote the dissociation of Cdc14 from its inhibitor, allowing the phosphatase to reach its targets throughout the cell. The molecular circuits that trigger the return of Cdc14 into the nucleolus after the completion of exit from mitosis are not known. Here we show that activation of a ubiquitin ligase known as the Anaphase-Promoting Complex or Cyclosome (APC/C) bound to the specificity factor Cdh1 triggers the degradation of the Polo kinase Cdc5, a key factor in releasing Cdc14 from its inhibitor in the nucleolus.

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Footnotes

↵4 Corresponding author.

↵4 E-MAIL rosella.visintin@ifom-ieo-campus.it; FAX 39-02-943-75-990.
Supplemental material is available at http://www.genesdev.org.
Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1601308
- Received August 6, 2007.
- Accepted October 31, 2007.