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Publication : Centrosome-associated NDR kinase regulates centrosome duplication.

First Author  Hergovich A Year  2007
Journal  Mol Cell Volume  25
Issue  4 Pages  625-34
PubMed ID  17317633 Mgi Jnum  J:119830
Mgi Id  MGI:3703312 Doi  10.1016/j.molcel.2007.01.020
Citation  Hergovich A, et al. (2007) Centrosome-associated NDR kinase regulates centrosome duplication. Mol Cell 25(4):625-34
abstractText  Human NDR kinases are upregulated in some cancer types, yet their functions still remain undefined. Here, we report the first known function of a mammalian NDR kinase by demonstrating that human NDR directly contributes to centrosome duplication. A subpopulation of endogenous NDR localizes to centrosomes in a cell-cycle-dependent manner. Overexpression of NDR resulted in centrosome overduplication in a kinase-activity-dependent manner, while expression of kinase-dead NDR or depletion of NDR by small interfering RNA (siRNA) negatively affected centrosome duplication. By targeting NDR to the centrosome, we show that the centrosomal pool of NDR is sufficient to generate supernumerary centrosomes. Furthermore, our data indicate that NDR-driven centrosome duplication requires Cdk2 activity and that Cdk2-induced centrosome amplification is affected upon reduction of NDR activity. Overall, considering that centrosome overduplication is linked to cellular transformation, our observations may also provide a molecular link between mammalian NDR kinases and cancer.
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