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Vol. 18, Issue 4, 1233-1241, April 2007

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Functional Interaction of Aurora-A and PP2A during Mitosis

Virginie Horn^*, Jacques Thélu^*, Alphonse Garcia, Corinne Albigès-Rizo^*, Marc R. Block^*, and Jean Viallet^*

*Institut Albert Bonniot, Centre de Recherche Institut National de la Santé et de la Recherche Médicale, Université Joseph Fourier U 823, Equipe DySAD, Université Joseph Fourier Site Santé, BP 170, F38042, Grenoble Cedex 09, France; and Equipe Phosphatase, Unité de Chimie Organique, Institut Pasteur, 75724 Paris Cedex, France

Submitted December 29, 2006; Accepted January 8, 2007
Monitoring Editor: John Pringle

Entry into mitosis is a highly regulated process, promoted by the activated Cyclin B1/Cdk1 complex. Activation of this complex is controlled, in part, by the protein kinase Aurora-A, which is a member of a multigenic serine/threonine kinase family. In normal cells, Aurora-A activity is regulated, at least in part, by degradation through the APC-ubiquitin-proteasome pathway. It has recently been proposed that, in Xenopus, Aurora-A degradation can be inhibited by phosphorylation. It would thus be expected that a phosphatase activity would release this blockade at the end of mitosis. Here, we have shown that the protein phosphatase PP2A and Aurora-A are colocalized at the cell poles during mitosis in human cells and interact within the same complex. Using the PP2A inhibitor okadaic acid and an RNAi approach, we have shown that this interaction is functional within the cell. PP2A/Aurora-A interaction is promoted by an S51D mutation in Aurora-A and inhibited by a phosphomimetic peptide centered around Aurora-A S51, thereby strongly suggesting that PP2A controls Aurora-A degradation by dephosphorylating serine 51 in the A box of the human enzyme.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Marc R. Block (marc.block{at}ujf-grenoble.fr)

Abbreviations used: MEM, Eagle's medium with alpha modification; DAPI, 4',6-diamidino-2-phenylindole; FACS, fluorescence-activated cell sorter; PP2A, protein phosphatase 2A; RNAi, RNA interference; siRNA, small interfering RNA.