| 2010 |
NEK10 physically associates with Raf-1 and MEK1 in a Raf-1-dependent manner upon UV irradiation. This complex formation is necessary for NEK10-mediated MEK1 activation. NEK10 does not affect Raf-1 kinase activity but instead promotes the autophosphorylation-dependent activation of MEK1, leading to ERK1/2 activation and G2/M checkpoint maintenance after UV damage. |
Co-immunoprecipitation, kinase activity assays, siRNA knockdown with cell cycle analysis |
Molecular and cellular biology |
Medium |
20956560
|
| 2010 |
NEK10 is required for ERK1/2 activation in response to UV irradiation but not in response to mitogens such as EGF, indicating a UV-specific function upstream of the MEK-ERK pathway. |
siRNA knockdown, immunoblot for phospho-ERK1/2 after UV or EGF stimulation |
Molecular and cellular biology |
Medium |
20956560
|
| 2020 |
NEK10 is a ciliated-cell-specific kinase whose activity regulates the motile ciliary proteome to promote ciliary length and mucociliary transport in primary human airway cultures; NEK10 loss does not affect ciliary number, radial structure, or beat frequency. |
Genetically modified primary human airway cultures (NEK10 loss-of-function), ciliary proteomics, mucociliary transport assay, electron microscopy |
Nature medicine |
High |
31959991
|
| 2020 |
NEK10 directly phosphorylates p53 on tyrosine 327 (Y327), and a p53-Y327F mutant acts as a hypomorph with attenuated transcriptional response. NEK10 loss increases cellular proliferation by modulating p53-dependent transcriptional output and causes heightened sensitivity to DNA-damaging agents. |
In vitro kinase assay with purified proteins, phospho-specific site mutagenesis (Y327F), transcriptional reporter assays, siRNA/CRISPR knockdown with proliferation and drug sensitivity assays |
Oncogene |
High |
32561851
|
| 2020 |
NEK10 interacts with mitochondria-associated proteins including SIRT3, ATAD3A, ATAD3B, and GLUD1 (confirmed by proximity ligation assay). NEK10 depletion causes mitochondrial fragmentation, altered mitochondrial ROS levels, decreased citrate synthase activity, inhibited mitochondrial respiration (particularly ATP-linked oxygen consumption and spare capacity), decreased mtDNA amplification ratio, and increased total mtDNA content. |
FLAG co-immunoprecipitation with LC-MS/MS proteomics, proximity ligation assay, confocal microscopy, stable shRNA knockdown, Seahorse respirometry, citrate synthase activity assay, mtDNA quantification |
Proteome science |
Medium |
32368190
|
| 2020 |
In C. elegans, NEKL-4 (NEK10 ortholog) localizes to the ciliary base but does not localize within cilia, suggesting an indirect role in ciliary processes. Loss-of-function of nekl-4 suppresses hyperglutamylation-induced ciliary degeneration in ccpp-1 mutants, placing NEKL-4 in a pathway modulating tubulin glutamylation effects. |
Forward genetic screen, fluorescence microscopy localization, epistasis analysis in C. elegans double mutants |
PLoS genetics |
Medium |
33064774
|
| 2024 |
NEK10 associates with the Axin destruction complex and phosphorylates β-catenin at Tyr30 (within the regulatory region governing β-catenin turnover). In the absence of NEK10-mediated Tyr30 phosphorylation, GSK3-mediated phosphorylation of β-catenin—a prerequisite for its degradation—is impaired, leading to β-catenin stabilization. NEK10-deficient lung adenocarcinoma cells show reduced tumorsphere formation, soft-agar growth, and lung colonization in vivo. |
CRISPR knockout, co-immunoprecipitation with Axin complex, in vitro kinase assay, site-specific mutagenesis, immunoblot for β-catenin phosphorylation/stability, tumorsphere assay, soft-agar assay, tail-vein injection mouse model |
Proceedings of the National Academy of Sciences of the United States of America |
High |
38683979
|
| 2024 |
NEK10 knockout in HAP1 cells alters threonine phosphorylation status of mitochondrial/ER proteins including HSP60, NDUFB4, and TOM20, and affects steady-state levels of respiratory complex proteins and autophagy pathway components, supporting a role for NEK10 in mitochondrial homeostasis via phosphorylation-dependent regulation. |
HAP1 NEK10 knockout cells, LC-MS/MS proteomics and phosphoproteomics of mitochondrial fractions, mitochondrial respiration assay, morphology analysis |
Proteome science |
Medium |
39379991
|
| 2025 |
NEK10 knockdown in tubular cells attenuates BSA-induced lipid droplet accumulation, G2/M arrest, and ERK1/2 phosphorylation, placing NEK10 upstream of ERK1/2 in an albumin-overload-driven metabolic and cell cycle disruption pathway; in vivo NEK10 knockdown (rAAV-shNEK10) reduces BSA-induced renal fibrosis in UUO mice. |
siRNA/rAAV shRNA knockdown in HK-2 cells and UUO mouse model, Western blotting for phospho-ERK1/2, flow cytometry cell cycle analysis, lipid droplet staining, fatty acid oxidation assay |
American journal of nephrology |
Low |
40934128
|
| 2026 |
ECM-derived mechanical forces reduce NEK10 expression via a cytoskeleton-dependent pathway, leading to suppression of the NEK10/p53/CDKN1A axis, activation of CDK2 signaling, and CDK4/6 inhibitor resistance in breast cancer cells. |
3D gel biomechanical models, scRNA-seq, transcriptomic analysis, Western blotting, NEK10-deficient cells/organoids, in vivo CDK2 inhibitor co-treatment |
International journal of surgery (London, England) |
Low |
41427545
|