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

dc.contributor.authorPaul, Swagatikaen
dc.contributor.authorSarraf, Shireenen
dc.contributor.authorNam, K. H.en
dc.contributor.authorZavar, Leilaen
dc.contributor.authorDeFoor, Nicoleen
dc.contributor.authorBiswas, Sahityaen
dc.contributor.authorFritsch, Laurenen
dc.contributor.authorYaron, Tomeren
dc.contributor.authorJohnson, Jareden
dc.contributor.authorHuntsman, Emilyen
dc.contributor.authorCantley, Lewisen
dc.contributor.authorOrdureau, Albanen
dc.contributor.authorPickrell, Alicia M.en
dc.date.accessioned2024-01-23T20:12:54Zen
dc.date.available2024-01-23T20:12:54Zen
dc.date.issued2023-12-07en
dc.description.abstractSubcellular 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.en
dc.description.versionPublished versionen
dc.format.extent31 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifierARTN e202303082 (Article number)en
dc.identifier.doihttps://doi.org/10.1083/jcb.202303082en
dc.identifier.eissn1540-8140en
dc.identifier.issn0021-9525en
dc.identifier.issue2en
dc.identifier.orcidPickrell, Alicia [0000-0002-8470-6056]en
dc.identifier.other276448 (PII)en
dc.identifier.pmid38059900en
dc.identifier.urihttps://hdl.handle.net/10919/117628en
dc.identifier.volume223en
dc.language.isoenen
dc.publisherRockefeller University Pressen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/38059900en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subject.meshHumansen
dc.subject.meshAdaptor Proteins, Signal Transducingen
dc.subject.meshCell Cycle Proteinsen
dc.subject.meshCell Cycleen
dc.subject.meshCytokinesisen
dc.subject.meshMitosisen
dc.subject.meshProtein Serine-Threonine Kinasesen
dc.titleNAK-associated protein 1/NAP1 activates TBK1 to ensure accurate mitosis and cytokinesisen
dc.title.serialJournal of Cell Biologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dcterms.dateAccepted2023-11-10en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Scienceen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Science/COS T&R Facultyen
pubs.organisational-group/Virginia Tech/Science/School of Neuroscienceen

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