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APC/Fizzy‐Related targets Aurora‐A kinase for proteolysis
Author(s) -
Castro Anna,
ArlotBonnemains Yannick,
Vigneron Suzanne,
Labbé JeanClaude,
Prigent Claude,
Lorca Thierry
Publication year - 2002
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1093/embo-reports/kvf095
Subject(s) - centrosome , aurora a kinase , microbiology and biotechnology , biology , mitosis , ectopic expression , xenopus , cell cycle , genetics , cell culture , cell , gene
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 (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.