PubMed Journals: J Cell Sci

  Source:		PMID: 15128871

    		J Cell Sci. 2004 May 15;117(Pt 12):2523-31.
     		Epub 2004 May 5.

			Phosphorylation of CDC25B by Aurora-A at
			the centrosome contributes to the G2-M transition.

			Dutertre S(1), Cazales M, Quaranta M, Froment
			C, Trabut V, Dozier C, Mirey G, Bouché JP,
			Theis-Febvre N, Schmitt E, Monsarrat B,
			Prigent C, Ducommun B.

			Author Information
			(1) Groupe Cycle Cellulaire - CNRS UMR6061
			- IFR97, Génomique Fonctionnelle et Santé,
			Université de Rennes I, 35043 Rennes, France.

			Aurora-A protein kinase, which is the product
			of an oncogene, is required for the assembly
			of a functional mitotic apparatus and the
			regulation of cell ploidy. Overexpression
			of Aurora-A in tumour cells has been correlated
			with cancer susceptibility and poor prognosis.
			Aurora-A activity is required for the recruitment
			of CDK1-cyclin B1 to the centrosome prior
			to its activation and the commitment of
			the cell to mitosis. In this report, we
			demonstrate that the CDC25B phosphatase,
			an activator of cyclin dependent kinases
			at mitosis, is phosphorylated both in vitro
			and in vivo by Aurora-A on serine 353 and
			that this phosphorylated form of CDC25B
			is located at the centrosome during mitosis.
			Knockdown experiments by RNAi confirm that
			the centrosome phosphorylation of CDC25B
			on S353 depends on Aurora-A kinase. Microinjection
			of antibodies against phosphorylated S353
			results in a mitotic delay whilst overexpression
			of a S353 phosphomimetic mutant enhances
			the mitotic inducing effect of CDC25B. Our
			results demonstrate that Aurora-A phosphorylates
			CDC25B in vivo at the centrosome during
			mitosis. This phosphorylation might locally
			participate in the control of the onset
			of mitosis. These findings re-emphasise
			the role of the centrosome as a functional
			integrator of the pathways contributing
			to the triggering of mitosis.

			DOI: 10.1242/jcs.01108 PMID: 15128871
			[Indexed for MEDLINE]

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