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J. Biol. Chem., Vol. 278, Issue 24, 21439-21449, June 13, 2003

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Cdc2-Cyclin B Triggers H3 Kinase Activation of Aurora-A in Xenopus Oocytes^*

Gilliane Maton , Catherine Thibier , Anna Castro  ¶, Thierry Lorca , Claude Prigent || and Catherine Jessus  **

From the Laboratoire de Biologie du Développement, Unite Mixte de Recherche-CNRS 7622, Université Pierre et Marie Curie, Boîte 24, 4 Place Jussieu, Paris 75252 cedex 05, Centre de Recherche de Biochimie Macromoléculaire, CNRS Unite Propre de Recherche 1086, 1919 Route de Mende, Montpellier 34293 cedex 5, ^|| Groupe Cycle Cellulaire, Unite Mixte de Recherche 6061 Génétique et Développement, CNRS-Université de Rennes I, Institut Federatif de Recherche 97, 2 Avenue du Pr. Léon Bernard, CS 34317, Rennes 35043 cedex, France

Xenopus oocytes are arrested in meiotic prophase I and resume meiotic divisions in response to progesterone. Progesterone triggers activation of M-phase promoting factor (MPF) or Cdc2-cyclin B complex and neosynthesis of Mos kinase, responsible for MAPK activation. Both Cdc2 and MAPK activities are required for the success of meiotic maturation. However, the signaling pathway induced by progesterone and leading to MPF activation is poorly understood, and most of the targets of both Cdc2 and MAPK in the oocyte remain to be determined. Aurora-A is a Ser/Thr kinase involved in separation of centrosomes and in spindle assembly during mitosis. It has been proposed that in Xenopus oocytes Aurora-A could be an early component of the progesterone-transduction pathway, acting through the regulation of Mos synthesis upstream Cdc2 activation. We addressed here the question of Aurora-A regulation during meiotic maturation by using new in vitro and in vivo experimental approaches. We demonstrate that Cdc2 kinase activity is necessary and sufficient to trigger both Aurora-A phosphorylation and kinase activation in Xenopus oocyte. In contrast, these events are independent of the Mos/MAPK pathway. Aurora-A is phosphorylated in vivo at least on three residues that regulate differentially its kinase activity. Therefore, Aurora-A is under the control of Cdc2 in the Xenopus oocyte and could be involved in meiotic spindle establishment.

Received for publication, January 24, 2003 , and in revised form, March 25, 2003.

^* This work was supported in part by the Institut de la Recherche Agronomique, CNRS, University of Paris VI and Paris XI, Association pour la Recherche Contre le Cancer (Grant 4771) and by the Ligue Nationale Contre le Cancer (to C. J. and T. L.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ A fellow of the Ligue Nationale Contre le Cancer.

^** To whom correspondence should be addressed. Tel.: 33-1-44-27-26-42; Fax: 33-1-44-27-34-72; E-mail: jessus{at}ccr.jussieu.fr.

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