Englander Institute for Precision Medicine

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

TitleNAK-associated protein 1/NAP1 activates TBK1 to ensure accurate mitosis and cytokinesis.
Publication TypeJournal Article
Year of Publication2024
AuthorsPaul S, Sarraf SA, Nam KHong, Zavar L, DeFoor N, Biswas SRanjan, Fritsch LE, Yaron TM, Johnson JL, Huntsman EM, Cantley LC, Ordureau A, Pickrell AM
JournalJ Cell Biol
Date Published2024 Feb 05
KeywordsAdaptor Proteins, Signal Transducing, Cell Cycle, Cell Cycle Proteins, Cytokinesis, Humans, Mitosis, Protein Serine-Threonine Kinases

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.

Alternate JournalJ Cell Biol
PubMed ID38059900
PubMed Central IDPMC10702366
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States
R35 GM142368 / GM / NIGMS NIH HHS / United States
GM142368 / NH / NIH HHS / United States

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