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

被引:133
作者
Castro, A
Arlot-Bonnemains, Y
Vigneron, S
Labbé, JC
Prigent, C
Lorca, T
机构
[1] CNRS, UPR 1086, Ctr Rech Biochim Macromol, F-34293 Montpellier 5, France
[2] Univ Rennes 1, CNRS, UMR Genet & Dev 6061, Grp Cycle Cellulaire, F-35043 Rennes, France
关键词
D O I
10.1093/embo-reports/kvf095
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 G(2)-M transistion and disappears completely at G(1) in XL2 cells. Using Xenopus oocyte extracts, we demonstrate that degradation of Aurora-A is mediated by the anaphase-promoting complex (APQ 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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页码:457 / 462
页数:6
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