Tank binding kinase 1 is a centrosome-associated kinase necessary for microtubule dynamics and mitosis

TANK Binding Kinase 1 (TBK1) is a non-canonical IκB kinase that contributes to KRAS-driven lung cancer. Here we report that TBK1 plays essential roles in mammalian cell division. Specifically, levels of active phospho-TBK1 increase during mitosis and localize to centrosomes, mitotic spindles and mid...

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Bibliographic Details
Published in:Nature communications 2015-12, Vol.6 (1), p.10072-10072, Article 10072
Main Authors: Pillai, Smitha, Nguyen, Jonathan, Johnson, Joseph, Haura, Eric, Coppola, Domenico, Chellappan, Srikumar
Format: Article
Language:English
Subjects:
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Cell Line
Centrosome - enzymology
Gene Expression Regulation, Enzymologic - physiology
Humanities and Social Sciences
Humans
Microtubules - physiology
Mitosis - physiology
multidisciplinary
Protein Binding
Protein Transport
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Science
Science (multidisciplinary)
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Summary:TANK Binding Kinase 1 (TBK1) is a non-canonical IκB kinase that contributes to KRAS-driven lung cancer. Here we report that TBK1 plays essential roles in mammalian cell division. Specifically, levels of active phospho-TBK1 increase during mitosis and localize to centrosomes, mitotic spindles and midbody, and selective inhibition or silencing of TBK1 triggers defects in spindle assembly and prevents mitotic progression. TBK1 binds to the centrosomal protein CEP170 and to the mitotic apparatus protein NuMA, and both CEP170 and NuMA are TBK1 substrates. Further, TBK1 is necessary for CEP170 centrosomal localization and binding to the microtubule depolymerase Kif2b, and for NuMA binding to dynein. Finally, selective disruption of the TBK1–CEP170 complex augments microtubule stability and triggers defects in mitosis, suggesting that TBK1 functions as a mitotic kinase necessary for microtubule dynamics and mitosis. TANK binding kinase 1 (TBK1) is a non-canonical IκB kinase that regulates immunity via NF-κB. Here Pillai et al . show that TBK1 localizes to centrosomes during mitosis, and regulates microtubule dynamics and spindle formation by phosphorylating the centrosomal protein CEP170 and the mitotic apparatus protein NuMa.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms10072