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APC/Fizzy-Related targets Aurora-A kinase for proteolysis
Anna Castro1, Yannick Arlot-Bonnemains, Suzanne Vigneron
1Centre de Recherche de Biochimie Macromoléculaire, CNRS UPR 1086, 1919 Route de Mende, F-34293 Montpellier Cedex 5, France.
EMBO Reports
|April 20, 2002
Summary
Aurora-A kinase degradation is controlled by the anaphase-promoting complex (APC) and Fizzy-Related, requiring a D-Box motif. This APC/Fizzy-Related pathway targets Aurora-A for destruction, impacting cell cycle regulation.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Aurora-A kinase is crucial for centrosome duplication, separation, and spindle assembly.
- Aberrant Aurora-A levels correlate with centrosome abnormalities and aneuploidy in mammalian cells.
Purpose of the Study:
- To investigate the regulatory mechanisms governing Aurora-A kinase degradation.
- To identify the specific pathway and motifs involved in Aurora-A protein turnover.
Main Methods:
- Utilized Xenopus oocyte extracts to study Aurora-A degradation.
- Employed site-directed mutagenesis to analyze the role of D-Box and KEN-Box motifs.
- Performed in vitro ubiquitilation assays with purified APC/Fizzy-Related complexes.
- Expressed Fizzy-Related ectopically in Xenopus oocytes.
Main Results:
- Aurora-A degradation is mediated by the anaphase-promoting complex (APC) and regulated by Fizzy-Related.
- Degradation is dependent on a D-Box motif, not the KEN-Box, on Aurora-A.
- APC/Fizzy-Related directly ubiquitylates Aurora-A.
- Ectopic Fizzy-Related expression leads to endogenous Aurora-A degradation.
Conclusions:
- Aurora-A undergoes D-Box-dependent degradation mediated by APC/Fizzy-Related.
- This pathway is distinct from APC/Fizzy-mediated degradation.
- Identified Aurora-A as the first protein degraded via this specific APC/Fizzy-Related pathway in the studied system.
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