ArticleHuman molecular genetics2012
The Nek8 protein kinase, mutated in the human cystic kidney disease nephronophthisis, is both activated and degraded during ciliogenesis.
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 70 citations in OpenAlex.
- Modeling Complex Developmental Disease: The Case of Polycystic Kidney Disease.Journal of developmental biology · 2026Review
- A divergent Plasmodium NEK4 acts as a key regulator driving the early events of meiosis.Nature communications · 2026Article
- A divergentResearch square · 2025Article
- NEK kinases in cell cycle regulation, DNA damage response, and cancer progression.Tissue & cell · 2025Review
- NEK8, a NIMA-family protein kinase at the core of the ciliary INV complex.Cell communication and signaling : CCS · 2025Review
- The NIMA-related kinase family and cancer.Frontiers in oncology · 2025Review
- Dimerization activates the Inversin complex inMolecular biology of the cell · 2024Article
- Glucosylceramide synthase modulation ameliorates murine renal pathologies and promotes macrophage effector function in vitro.Communications biology · 2024Article
- Illumination of understudied ciliary kinases.Frontiers in molecular biosciences · 2024Review
- Conserved NIMA kinases regulate multiple steps of endocytic trafficking.PLoS genetics · 2023Article
- The NEK family of serine/threonine kinases as a biomarker for cancer.Clinical and experimental medicine · 2023Review
- A comprehensive transcriptomic analysis of the bisphenol A affected kidney in mice.Frontiers in molecular biosciences · 2023Article
- In Mitosis You Are Not: The NIMA Family of Kinases inInternational journal of molecular sciences · 2022Review
- Whole-Exome Sequencing Identifies the VHL Mutation (c.262T > C, p.Try88Arg) in Non-Obstructive Azoospermia-Associated Cystic Renal Cell CarcinomaCurrent oncology (Toronto, Ont.) · 2022Article
- Novel variants ofFrontiers in genetics · 2022Article
- Never-in-Mitosis A-Related Kinase 8 (NEK8) Regulates Adipogenesis, Glucose Homeostasis, and Obesity.Oxidative medicine and cellular longevity · 2022Article
- Nephronophthisis-Pathobiology and Molecular Pathogenesis of a Rare Kidney Genetic Disease.Genes · 2021Review
- Bioinformatics analysis of the prognostic value of NEK8 and its effects on immune cell infiltration in glioma.Journal of cellular and molecular medicine · 2021Article
- Polyglutamylase activity of tubulin tyrosine ligase-like 4 is negatively regulated by the never in mitosis gene A family kinase never in mitosis gene A -related kinase 5.World journal of biological chemistry · 2021Article
- Investigation of candidate genes and mechanisms underlying obesity associated type 2 diabetes mellitus using bioinformatics analysis and screening of small drug molecules.BMC endocrine disorders · 2021Article
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3 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in the never-in-mitosis A-related kinase, Nek8, are associated with cystic kidney disease in both humans and mice, with Nek8 being the NPHP9 gene in the human juvenile cystic kidney disease, nephronophthisis. Human Nek8/NPHP9 localizes to centrosomes and the proximal region of cilia in dividing and ciliated cells, respectively. However, the regulation of Nek8 kinase activity, as well as its role in ciliogenesis, remains to be defined. Here, by establishing Nek8 kinase assays, we first demonstrate that the localization of Nek8 to centrosomes and cilia is dependent on both kinase activity and the C-terminal non-catalytic RCC1 domain. The kinase domain alone is active, but does not localize correctly, while the RCC1 domain localizes correctly and can be phosphorylated by Nek8. We propose that centrosome recruitment is mediated by the RCC1 domain, but requires a conformational change in the full-length protein that is promoted by autophosphorylation. Interestingly, three human NPHP9-associated mutants retain full kinase activity. However, only two of these, L330F and A497P, localize correctly, suggesting that the third mutant, H425Y, disrupts a centrosome targeting sequence in the RCC1 domain. Importantly, we find that induction of ciliogenesis upon cell cycle exit is accompanied by both activation and proteasomal degradation of Nek8, and that activation is dependent upon phosphorylation within the catalytic domain. Taken together, these findings reveal important insights into the mechanisms through which Nek8 activity and localization are regulated during ciliogenesis.
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