NAK-associated protein 1/NAP1 activates TBK1 to ensure accurate mitosis and cytokinesis

Swagatika Paul, Shireen A. Sarraf, Ki Hong Nam, Leila Zavar, Nicole Defoor, Sahitya Ranjan Biswas, Lauren E. Fritsch, Tomer M. Yaron, Jared L. Johnson, Emily M. Huntsman, Lewis C. Cantley, Alban Ordureau, Alicia M. Pickrell

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Subcellular location and activation of Tank Binding Kinase 1 (TBK1) govern precise progression through mitosis. Either loss of activated TBK1 or its sequestration from the centrosomes causes errors in mitosis and growth defects. Yet, what regulates its recruitment and activation on the centrosomes is unknown. We identified that NAK-associated protein 1 (NAP1) is essential for mitosis, binding to and activating TBK1, which both localize to centrosomes. Loss of NAP1 causes several mitotic and cytokinetic defects due to inactivation of TBK1. Our quantitative phosphoproteomics identified numerous TBK1 substrates that are not only confined to the centrosomes but are also associated with microtubules. Substrate motifs analysis indicates that TBK1 acts upstream of other essential cell cycle kinases like Aurora and PAK kinases. We also identified NAP1 as a TBK1 substrate phosphorylating NAP1 at S318 to promote its degradation by the ubiquitin proteasomal system. These data uncover an important distinct function for the NAP1–TBK1 complex during cell division.

Original languageEnglish
Article numbere202303082
JournalJournal of Cell Biology
Volume223
Issue number2
DOIs
StatePublished - 5 Feb 2024
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2024, Rockefeller University Press. All rights reserved.

Funding

This work was supported by the National Institutes of Health Grants GM142368 (A.M. Pickrell) and departmental startup funds (A.M. Pickrell).

FundersFunder number
National Institutes of HealthGM142368

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