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EMBO reports 3, 5, 457–462 (2002)
doi:10.1093/embo-reports/kvf095
Published online: May 2002
APC/Fizzy-Related targets Aurora-A kinase for proteolysis
Anna Castro1, Yannick Arlot-Bonnemains2, Suzanne Vigneron1, Jean-Claude Labbé1, Claude Prigent2 & Thierry Lorca1
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1 Centre de Recherche de Biochimie Macromoléculaire, CNRS UPR 1086, 1919 Route de Mende, F-34293 Montpellier Cedex 5 France
2 Groupe Cycle Cellulaire, UMR 6061 Génétique et Dévelopement, CNRS-Université de Rennes I, IFR 97, 2 Avenue du Pr Léon Bernard, F-35043 Rennes, France
To whom correspondence should be addressed
Thierry Lorca Tel: +33 4 6761 3328; Fax: +33 4 6752 1559; lorca@crbm.cnrs-mop.fr
Received 6 February 2002; Accepted 15 March 2002.
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Abstract
Aurora-A kinase is a mitotic spindle-pole-associated protein that has been implicated in duplication and separation of centrosomes and in spindle assembly. The proper timing and amplitude of Aurora-A expression seems to be important, as elevated levels of this protein have been associated with centrosome abnormalities and aneuploidy in mammalian cells. We show that Aurora-A increases at the G2–M transistion and disappears completely at G1 in XL2 cells. Using Xenopus oocyte extracts, we demonstrate that degradation of Aurora-A is mediated by the anaphase-promoting complex (APC) and is regulated by Fizzy-Related but not by Fizzy. Degradation of Aurora-A depends on a D-Box, but not on its KEN-Box motif, as mutation of its C-terminal D-Box sequence induces stabilization of the protein. Accordingly, addition into the extracts of a cyclin B-type D-Box-motif-containing peptide completely suppresses its degradation. Furthermore, APC/Fizzy-Related ubiquitylates the wild type but not a D-Box mutant form of Aurora-A in vitro. Consistent with these data, ectopic expression of Fizzy-Related in Xenopus oocytes induces complete degradation of endogenous Aurora-A. Aurora-A is thus the first protein, at least in our assay system, that undergoes a D-Box-dependent degradation mediated by APC/Fizzy-Related but not by APC/Fizzy.
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