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

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  • Anna Castro
    Centre de Recherche de Biochimie Macromoléculaire, CNRS UPR 1086 1919 Route de Mende F‐34293 Montpellier Cedex 5 France
  • Yannick Arlot‐Bonnemains
    Groupe Cycle Cellulaire, UMR 6061 Génétique et Dévelopement, CNRS‐Université de Rennes I, IFR 97 2 Avenue du Pr Léon Bernard F‐35043 Rennes France
  • Suzanne Vigneron
    Centre de Recherche de Biochimie Macromoléculaire, CNRS UPR 1086 1919 Route de Mende F‐34293 Montpellier Cedex 5 France
  • Jean‐Claude Labbé
    Centre de Recherche de Biochimie Macromoléculaire, CNRS UPR 1086 1919 Route de Mende F‐34293 Montpellier Cedex 5 France
  • Claude Prigent
    Groupe Cycle Cellulaire, UMR 6061 Génétique et Dévelopement, CNRS‐Université de Rennes I, IFR 97 2 Avenue du Pr Léon Bernard F‐35043 Rennes France
  • Thierry Lorca
    Centre de Recherche de Biochimie Macromoléculaire, CNRS UPR 1086 1919 Route de Mende F‐34293 Montpellier Cedex 5 France

抄録

<jats:p>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<jats:sub>2</jats:sub>–M transistion and disappears completely at G<jats:sub>1</jats:sub> in XL2 cells. Using <jats:italic>Xenopus</jats:italic> 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 <jats:italic>in vitro</jats:italic>. Consistent with these data, ectopic expression of Fizzy‐Related in <jats:italic>Xenopus</jats:italic> 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.</jats:p>

収録刊行物

  • EMBO reports

    EMBO reports 3 (5), 457-462, 2002-05

    Springer Science and Business Media LLC

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