ArticleMolecular and cellular biology2012
Nek4 regulates entry into replicative senescence and the response to DNA damage in human fibroblasts.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
41 citing papers in PubMed, 54 citations in OpenAlex.
- Construction and Validation of Plasma Protein-Based Musculoskeletal Biological Age and Genetic and Environmental Risk Profiles.Aging cell · 2026Article
- Phosphosite-specific co-regulation networks of MELK kinase: insights from integrative global phosphoproteomes.Journal, genetic engineering & biotechnology · 2026Article
- Systematic Evaluation Defines the Limits of Ferroptosis in Cancer Therapy.bioRxiv : the preprint server for biology · 2026Article
- Structural variations in evolutionary novel genomic regions: new insights into neurodevelopmental disorders by long-read DNA Sequencing.Molecular medicine (Cambridge, Mass.) · 2026Article
- NEK Family Kinases: Structure, Function, and Role in Disease.Biomolecules · 2025Review
- NEK kinases in cell cycle regulation, DNA damage response, and cancer progression.Tissue & cell · 2025Review
- NEK4 suppresses cell proliferation in BT20 triple-negative breast cancer cells by diminishing expression of cell cycle genes, while its depletion mitigates proliferation in other cell lines.Frontiers in oncology · 2025Article
- The emerging role of Never-in-Mitosis A - Related Kinases in the endothelium.The international journal of biochemistry & cell biology · 2024Review
- The Mitochondrial Connection: The Nek Kinases' New Functional Axis in Mitochondrial Homeostasis.Cells · 2024Review
- Differential Expression of NEK Kinase Family Members in Esophageal Adenocarcinoma and Barrett's Esophagus.Cancers · 2023Article
- Transcriptome-wide association study identifies novel candidate susceptibility genes for migraine.HGG advances · 2023Article
- Elephants as an animal model for self-domestication.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- NEK Family Review and Correlations with Patient Survival Outcomes in Various Cancer Types.Cancers · 2023Review
- Article
- In Mitosis You Are Not: The NIMA Family of Kinases inInternational journal of molecular sciences · 2022Review
- Analysis of the effect of NEKs on the prognosis of patients with non-small-cell lung carcinoma based on bioinformatics.Scientific reports · 2022Article
- NEK1 deficiency affects mitochondrial functions and the transcriptome of key DNA repair pathways.Mutagenesis · 2021Article
- Review
- New Insights Into Human Hyaluronidase 4/Chondroitin Sulphate Hydrolase.Frontiers in cell and developmental biology · 2021Review
- Targeting NEK2 impairs oncogenesis and radioresistance via inhibiting the Wnt1/β-catenin signaling pathway in cervical cancer.Journal of experimental & clinical cancer research : CR · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
When explanted into culture, normal human cells exhibit a finite number of cell divisions before entering a proliferative arrest termed replicative senescence. To identify genes essential for entry into replicative senescence, we performed an RNA interference (RNAi)-based loss-of-function screen and found that suppression of the Never in Mitosis Gene A (NIMA)-related protein kinase gene NEK4 disrupted timely entry into senescence. NEK4 suppression extended the number of population doublings required to reach replicative senescence in several human fibroblast strains and resulted in decreased transcription of the cyclin-dependent kinase inhibitor p21. NEK4-suppressed cells displayed impaired cell cycle arrest in response to double-stranded DNA damage, and mass spectrometric analysis of Nek4 immune complexes identified a complex containing DNA-dependent protein kinase catalytic subunit [DNA-PK(cs)], Ku70, and Ku80. NEK4 suppression causes defects in the recruitment of DNA-PK(cs) to DNA upon induction of double-stranded DNA damage, resulting in reduced p53 activation and H2AX phosphorylation. Together, these observations implicate Nek4 as a novel regulator of replicative senescence and the response to double-stranded DNA damage.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.