1. NAK-associated protein 1/NAP1 activates TBK1 to ensure accurate mitosis and cytokinesis.
- Author
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Paul S, Sarraf SA, Nam KH, Zavar L, DeFoor N, Biswas SR, Fritsch LE, Yaron TM, Johnson JL, Huntsman EM, Cantley LC, Ordureau A, and Pickrell AM
- Subjects
- Humans, Cell Cycle, Cell Cycle Proteins genetics, Cell Cycle Proteins metabolism, Cytokinesis, Mitosis, Adaptor Proteins, Signal Transducing genetics, Adaptor Proteins, Signal Transducing metabolism, Protein Serine-Threonine Kinases genetics, Protein Serine-Threonine Kinases metabolism
- 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., (This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.)
- Published
- 2024
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