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EMBO reports 3, 12, 1209–1214 (2002)
doi:10.1093/embo-reports/kvf241
Published online: December 2002
The D-Box-activating domain (DAD) is a new proteolysis signal that stimulates the silent D-Box sequence of Aurora-A
Anna Castro1, Suzanne Vigneron1, Cyril Bernis1, 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, 34293 Montpellier cedex 5, France
2 Groupe Cycle Cellulaire, UMR 6061 Génétique et Développement, CNRS-Université de Rennes I, IFR 97, 2 Avenue du Pr Léon Bernard, 35043 Rennes, France
To whom correspondence should be addressed
Thierry Lorca Fax: +33 4 67 52 15 59; lorca@crbm.cnrs-mop.fr
Received 29 August 2002; Accepted 15 October 2002.
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Abstract
We have demonstrated previously that Xenopus Aurora-A is degraded at late mitosis by the APC/Fizzy-Related in a D-Box-dependent manner. Here we demonstrate that, although Aurora-B possesses the same D-Box as Aurora-A, Aurora-B is not degraded by this ubiquitin ligase. We have constructed a chimera Aurora-A/B with the N-terminus of Aurora-A and the C-terminus of Aurora-B and we have examined its degradation by APC/Fizzy-Related. We demonstrate that the N-terminus of Aurora-A confers degradation capacity on the C-terminus of Aurora-B and that this feature is blocked by mutation of the conserved D-Box sequence. We characterize the minimal degradation signal at the N-terminus of Aurora-A and demonstrate that its deletion blocks the degradation of this protein by APC/Fizzy-Related. Thus, we conclude that two different degradation signals are required for proteolysis of Aurora-A. The first one, which we designated D-Box-activating domain, within the N-terminal domain of Aurora-A confers the functionality to the second, a silent D-Box, present within the C-terminus of the kinase.
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