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Functional interaction of Aurora-A and PP2A during mitosis.
Horn V
,
Thélu J
,
Garcia A
,
Albigès-Rizo C
,
Block MR
,
Viallet J
.
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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.
Anand,
AURORA-A amplification overrides the mitotic spindle assembly checkpoint, inducing resistance to Taxol.
2003, Pubmed
Anand,
AURORA-A amplification overrides the mitotic spindle assembly checkpoint, inducing resistance to Taxol.
2003,
Pubmed
Andersen,
Proteomic characterization of the human centrosome by protein correlation profiling.
2003,
Pubmed
Bialojan,
Inhibitory effect of a marine-sponge toxin, okadaic acid, on protein phosphatases. Specificity and kinetics.
1988,
Pubmed
Bischoff,
The Aurora/Ipl1p kinase family: regulators of chromosome segregation and cytokinesis.
1999,
Pubmed
Blagden,
Polar expeditions--provisioning the centrosome for mitosis.
2003,
Pubmed
Chaudhuri,
Effects of low concentrations of okadaic acid in HeLa cells.
1997,
Pubmed
Chen,
Identification of specific PP2A complexes involved in human cell transformation.
2004,
Pubmed
Dai,
Polo-like kinases in cell cycle checkpoint control.
2003,
Pubmed
,
Xenbase
Eyers,
Regulating the regulators: Aurora A activation and mitosis.
2003,
Pubmed
,
Xenbase
Francisco,
Regulation of yeast chromosome segregation by Ipl1 protein kinase and type 1 protein phosphatase.
1994,
Pubmed
Glover,
Mutations in aurora prevent centrosome separation leading to the formation of monopolar spindles.
1995,
Pubmed
Goepfert,
The centrosome-associated Aurora/Ipl-like kinase family.
2000,
Pubmed
Goepfert,
Centrosome amplification and overexpression of aurora A are early events in rat mammary carcinogenesis.
2002,
Pubmed
,
Xenbase
Gopalan,
A novel mammalian, mitotic spindle-associated kinase is related to yeast and fly chromosome segregation regulators.
1997,
Pubmed
Healy,
CDC55, a Saccharomyces cerevisiae gene involved in cellular morphogenesis: identification, characterization, and homology to the B subunit of mammalian type 2A protein phosphatase.
1991,
Pubmed
Helps,
NIMA-related kinase 2 (Nek2), a cell-cycle-regulated protein kinase localized to centrosomes, is complexed to protein phosphatase 1.
2000,
Pubmed
Hemmings,
alpha- and beta-forms of the 65-kDa subunit of protein phosphatase 2A have a similar 39 amino acid repeating structure.
1990,
Pubmed
Hirota,
Aurora-A and an interacting activator, the LIM protein Ajuba, are required for mitotic commitment in human cells.
2003,
Pubmed
,
Xenbase
Honda,
Degradation of human Aurora2 protein kinase by the anaphase-promoting complex-ubiquitin-proteasome pathway.
2000,
Pubmed
Kallioniemi,
Detection and mapping of amplified DNA sequences in breast cancer by comparative genomic hybridization.
1994,
Pubmed
Karaïskou,
Phosphatase 2A and polo kinase, two antagonistic regulators of cdc25 activation and MPF auto-amplification.
1999,
Pubmed
,
Xenbase
Katayama,
Interaction and feedback regulation between STK15/BTAK/Aurora-A kinase and protein phosphatase 1 through mitotic cell division cycle.
2001,
Pubmed
Khew-Goodall,
Tissue-specific expression of mRNAs encoding alpha- and beta-catalytic subunits of protein phosphatase 2A.
1988,
Pubmed
Lechward,
Protein phosphatase 2A: variety of forms and diversity of functions.
2001,
Pubmed
Lee,
The role of protein phosphatase type-2A in the Xenopus cell cycle: initiation of the G2/M transition.
1995,
Pubmed
,
Xenbase
Littlepage,
Identification of a new APC/C recognition domain, the A box, which is required for the Cdh1-dependent destruction of the kinase Aurora-A during mitotic exit.
2002,
Pubmed
,
Xenbase
Liu,
Aurora A, mitotic entry, and spindle bipolarity.
2006,
Pubmed
,
Xenbase
Mailhes,
Okadaic acid, an inhibitor of protein phosphatase 1 and 2A, induces premature separation of sister chromatids during meiosis I and aneuploidy in mouse oocytes in vitro.
2003,
Pubmed
Marumoto,
Roles of aurora-A kinase in mitotic entry and G2 checkpoint in mammalian cells.
2002,
Pubmed
,
Xenbase
Maton,
Differential regulation of Cdc2 and Aurora-A in Xenopus oocytes: a crucial role of phosphatase 2A.
2005,
Pubmed
,
Xenbase
Mayer,
Expression and organization of protein phosphatase 2A catalytic subunit genes.
1990,
Pubmed
Mayer,
Structure of the 55-kDa regulatory subunit of protein phosphatase 2A: evidence for a neuronal-specific isoform.
1991,
Pubmed
Meraldi,
Aurora kinases link chromosome segregation and cell division to cancer susceptibility.
2004,
Pubmed
Minshull,
Protein phosphatase 2A regulates MPF activity and sister chromatid cohesion in budding yeast.
1996,
Pubmed
Price,
Effects of regulatory subunits on the kinetics of protein phosphatase 2A.
2000,
Pubmed
Rieder,
The centrosome in vertebrates: more than a microtubule-organizing center.
2001,
Pubmed
Schlegel,
Comparative genomic in situ hybridization of colon carcinomas with replication error.
1995,
Pubmed
Sen,
A putative serine/threonine kinase encoding gene BTAK on chromosome 20q13 is amplified and overexpressed in human breast cancer cell lines.
1997,
Pubmed
Strack,
Protein phosphatase 2A holoenzyme assembly: identification of contacts between B-family regulatory and scaffolding A subunits.
2002,
Pubmed
Strack,
Cloning and characterization of B delta, a novel regulatory subunit of protein phosphatase 2A.
1999,
Pubmed
Tournebize,
Distinct roles of PP1 and PP2A-like phosphatases in control of microtubule dynamics during mitosis.
1997,
Pubmed
,
Xenbase
Virshup,
Protein phosphatase 2A: a panoply of enzymes.
2000,
Pubmed
Zolnierowicz,
Diversity in the regulatory B-subunits of protein phosphatase 2A: identification of a novel isoform highly expressed in brain.
1994,
Pubmed
Zolnierowicz,
Protein phosphorylation and protein phosphatases. De Panne, Belgium, September 19-24, 1999.
2000,
Pubmed
