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

Author

Listed:
  • Smitha Pillai

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Jonathan Nguyen

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Joseph Johnson

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Eric Haura

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Domenico Coppola

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Srikumar Chellappan

    (H. Lee Moffitt Cancer Center and Research Institute)

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.

Suggested Citation

  • Smitha Pillai & Jonathan Nguyen & Joseph Johnson & Eric Haura & Domenico Coppola & Srikumar Chellappan, 2015. "Tank binding kinase 1 is a centrosome-associated kinase necessary for microtubule dynamics and mitosis," Nature Communications, Nature, vol. 6(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms10072
    DOI: 10.1038/ncomms10072
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    Cited by:

    1. Daipayan Banerjee & Kurt Langberg & Salar Abbas & Eric Odermatt & Praveen Yerramothu & Martin Volaric & Matthew A. Reidenbach & Kathy J. Krentz & C. Dustin Rubinstein & David L. Brautigan & Tarek Abba, 2021. "A non-canonical, interferon-independent signaling activity of cGAMP triggers DNA damage response signaling," Nature Communications, Nature, vol. 12(1), pages 1-24, December.

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