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.
(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]