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APC/Fizzy-Related targets Aurora-A kinase for proteolysis.

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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https://www.hal.inserm.fr/inserm-00966246
Contributor : Claude Prigent <>
Submitted on : Wednesday, March 26, 2014 - 12:28:29 PM
Last modification on : Wednesday, May 16, 2018 - 11:23:33 AM

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Anna Castro, Yannick Arlot-Bonnemains, Suzanne Vigneron, Jean-Claude Labbé, Claude Prigent, et al.. APC/Fizzy-Related targets Aurora-A kinase for proteolysis.. EMBO Reports, EMBO Press, 2002, 3 (5), pp.457-62. ⟨10.1093/embo-reports/kvf095⟩. ⟨inserm-00966246⟩

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