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Molecular Cell
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Molecular Cell
Article . 2007
License: Elsevier Non-Commercial
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Molecular Cell
Article . 2007 . Peer-reviewed
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Molecular Cell
Article . 2007
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Centrosome-Associated NDR Kinase Regulates Centrosome Duplication

Authors: Hergovich, Alexander; Lamla, Stefan; Nigg, Erich A.; Hemmings, Brian A.;

Centrosome-Associated NDR Kinase Regulates Centrosome Duplication

Abstract

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.

Country
Switzerland
Keywords

Centrosome, Cyclin-Dependent Kinase 2, Gene Expression, Cell Biology, CHO Cells, Protein Serine-Threonine Kinases, Protein-Serine-Threonine Kinases, HCT116 Cells, Mice, Protein Transport, Cricetulus, Cricetinae, COS Cells, Chlorocebus aethiops, NIH 3T3 Cells, Animals, Humans, Molecular Biology, HeLa Cells, Protein Binding

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    selected citations
    These citations are derived from selected sources.
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    103
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
103
Top 10%
Top 10%
Top 10%
hybrid
Related to Research communities
Cancer Research