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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Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 26, 2002, 6:57 p.m.) |
Deposited | 1 year, 8 months ago (Dec. 18, 2023, 3:56 p.m.) |
Indexed | 3 weeks, 5 days ago (Aug. 5, 2025, 8:10 a.m.) |
Issued | 23 years, 4 months ago (May 1, 2002) |
Published | 23 years, 4 months ago (May 1, 2002) |
Published Online | 23 years, 4 months ago (May 1, 2002) |
Published Print | 23 years, 4 months ago (May 1, 2002) |
@article{Castro_2002, title={APC/Fizzy‐Related targets Aurora‐A kinase for proteolysis}, volume={3}, ISSN={1469-3178}, url={http://dx.doi.org/10.1093/embo-reports/kvf095}, DOI={10.1093/embo-reports/kvf095}, number={5}, journal={EMBO reports}, publisher={Springer Science and Business Media LLC}, author={Castro, Anna and Arlot‐Bonnemains, Yannick and Vigneron, Suzanne and Labbé, Jean‐Claude and Prigent, Claude and Lorca, Thierry}, year={2002}, month=may, pages={457–462} }