Centrosome-associated NDR kinase regulates centrosome duplication.
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.
Hergovich
Alexander
A
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
Lamla
Stefan
S
Nigg
Erich A
EA
Hemmings
Brian A
BA
D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D018385:Centrosome / Q000201:enzymology*; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D015870:Gene Expression; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport
D017346:Protein Serine-Threonine Kinases; C491614:STK38 protein, human; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2