The D-Box-activating Domain (DAD) is a New Proteolysis Signal That Stimulates the Silent D-Box Sequence of Aurora-A

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2002 Nov 26

PMID 12446569

Citations 33

Authors

Anna Castro

Suzanne Vigneron

Cyril Bernis

Jean-Claude Labbe

Claude Prigent

Thierry Lorca

Affiliations

Soon will be listed here.

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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