Functional interaction of Aurora-A and PP2A during mitosis.
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.
Horn
Virginie
V
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.
Thélu
Jacques
J
Garcia
Alphonse
A
Albigès-Rizo
Corinne
C
Block
Marc R
MR
Viallet
Jean
J
D000818:Animals; D064127:Aurora Kinases; D016466:CHO Cells; D020134:Catalytic Domain; D018385:Centrosome / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits; D012694:Serine / Q000235:genetics / Q000378:metabolism
D004791:Enzyme Inhibitors; D021122:Protein Subunits; D019319:Okadaic Acid; D012694:Serine; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D010749:Phosphoprotein Phosphatases