title: Tank binding kinase 1 is a centrosome-associated kinase necessary for microtubule dynamics and mitosis.
abstract: 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.
authors.affiliation: Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USA.
authors.forename: Smitha
authors.initials: S
authors.lastname: Pillai
authors.affiliation: Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USA.
authors.forename: Jonathan
authors.identifier: http://orcid.org/0000-0001-6146-2047
authors.initials: J
authors.lastname: Nguyen
authors.affiliation: Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Johnson
authors.affiliation: Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Haura
authors.affiliation: Department of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USA.
authors.forename: Domenico
authors.initials: D
authors.lastname: Coppola
authors.affiliation: Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, USA.
authors.forename: Srikumar
authors.identifier: http://orcid.org/0000-0003-1216-2966
authors.initials: S
authors.lastname: Chellappan
mesh_terms: D002460:Cell Line; D018385:Centrosome / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D008870:Microtubules / Q000502:physiology*; D008938:Mitosis / Q000502:physiology*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport
chemical_list: D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human