NEK10, a serine/threonine/tyrosine kinase belonging to the NEK (NIMA-related kinases) family, is involved in multiple biological processes. It has been associated with DNA damage response, cell cycle regulation, mitochondrial homeostasis, and mucociliary clearance [1,2,3,5]. Genetic models, such as knockout models, are valuable in studying its functions.

In gene knockout studies, NEK10-deficient cells show increased cellular proliferation due to modulation of p53-dependent transcriptional output as NEK10 directly phosphorylates p53 on Y327 [1]. Also, NEK10-depleted cells display more fragmented mitochondria, changes in mitochondrial reactive oxygen species levels, decreased citrate synthase activity, and inhibited mitochondrial respiration, suggesting its role in mitochondrial homeostasis [2,3]. In lung adenocarcinoma cells, deletion of Nek10 leads to β-catenin stabilization, affecting tumor-related abilities like tumorsphere formation and soft agar growth [4]. In humans, mutations inactivating NEK10 cause a bronchiectasis syndrome, and in vitro studies with genetically modified primary human airway cultures show it is a ciliated-cell-specific kinase regulating ciliary length and mucociliary transport [5].

In conclusion, NEK10 plays essential roles in DNA damage response, mitochondrial function, cell cycle regulation, and mucociliary clearance. Gene knockout models have been crucial in revealing these functions, especially in relation to diseases such as cancer and bronchiectasis. Understanding NEK10 functions provides insights into disease mechanisms and potential therapeutic targets.

References:

1. Haider, Nasir, Dutt, Previn, van de Kooij, Bert, Yaffe, Michael, Stambolic, Vuk. 2020. NEK10 tyrosine phosphorylates p53 and controls its transcriptional activity. In Oncogene, 39, 5252-5266. doi:10.1038/s41388-020-1361-x. https://pubmed.ncbi.nlm.nih.gov/32561851/

2. Peres de Oliveira, Andressa, Basei, Fernanda Luisa, Slepicka, Priscila Ferreira, Menck, Carlos Frederico Martins, Kobarg, Jörg. 2020. NEK10 interactome and depletion reveal new roles in mitochondria. In Proteome science, 18, 4. doi:10.1186/s12953-020-00160-w. https://pubmed.ncbi.nlm.nih.gov/32368190/

3. de Oliveira, Andressa Peres, Navarro, Claudia D C, Dias, Pedro Rafael F, Moraes, Carlos T, Kobarg, Jörg. 2024. NEK10 kinase ablation affects mitochondrial morphology, function and protein phosphorylation status. In Proteome science, 22, 8. doi:10.1186/s12953-024-00234-z. https://pubmed.ncbi.nlm.nih.gov/39379991/

4. Dutt, Previn, Haider, Nasir, Mouaaz, Samar, Podmore, Lauren, Stambolic, Vuk. 2024. β-catenin turnover is regulated by Nek10-mediated tyrosine phosphorylation in A549 lung adenocarcinoma cells. In Proceedings of the National Academy of Sciences of the United States of America, 121, e2300606121. doi:10.1073/pnas.2300606121. https://pubmed.ncbi.nlm.nih.gov/38683979/

5. Chivukula, Raghu R, Montoro, Daniel T, Leung, Hui Min, Alkuraya, Fowzan S, Sabatini, David M. 2020. A human ciliopathy reveals essential functions for NEK10 in airway mucociliary clearance. In Nature medicine, 26, 244-251. doi:10.1038/s41591-019-0730-x. https://pubmed.ncbi.nlm.nih.gov/31959991/