ArticlePloS one2012
Cyclin-dependent kinase 6 phosphorylates NF-κB P65 at serine 536 and contributes to the regulation of inflammatory gene expression.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed.
- Cell-cycle targeted cancer therapy: clinical advances, biological gaps, and the emergence of selective CDK4 inhibitors.Journal of hematology & oncology · 2026Review
- MiR-181a-5p/CDK6 axis attenuates cell proliferation, migration and glycolytic reprogramming in oral squamous cell carcinoma.Cancer cell international · 2026Article
- BET Bromodomain Inhibition Reverses CDK4/6 Inhibitor Resistance in Estrogen Receptor-Positive Breast Cancer via Induction of miR-34a-5p.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Downregulation of the NF-κB protein p65 is a shared phenotype among most anti-aging interventions.GeroScience · 2025Article
- Cyclin-dependent protein kinases and cell cycle regulation in biology and disease.Signal transduction and targeted therapy · 2025Review
- Melatonin Ameliorate neuroinflammation in activated microglia through the Aryl hydrocarbon-Nrf2 axis.International journal of biological sciences · 2025Article
- A Two-Sample Mendelian Randomization Study of Basophil Count and Risk of Gestational Diabetes Mellitus.International journal of women's health · 2025Article
- Rafoxanide negatively modulates STAT3 and NF-κB activity and inflammation-associated colon tumorigenesis.Cancer science · 2024Article
- DNA hypomethylation activates Cdk4/6 and Atr to induce DNA replication and cell cycle arrest to constrain liver outgrowth in zebrafish.Nucleic acids research · 2024Article
- Senotherapeutics to Counteract Senescent Cells Are Prominent Topics in the Context of Anti-Ageing Strategies.International journal of molecular sciences · 2024Review
- Post-translational modifications of p65: state of the art.Frontiers in cell and developmental biology · 2024Review
- Potential Target of CDK6 Signaling Pathway for Cancer Treatment.Current drug targets · 2024Review
- Cyclin-dependent kinases: Masters of the eukaryotic universe.Wiley interdisciplinary reviews. RNA · 2023Review
- Repeated Episodes of Ischemia/Reperfusion Induce Heme-Oxygenase-1 (HO-1) and Anti-Inflammatory Responses and Protects against Chronic Kidney Disease.International journal of molecular sciences · 2022Article
- Platelet factor 4 (CXCL4/PF4) upregulates matrix metalloproteinase-2 (MMP-2) in gingival fibroblasts.Scientific reports · 2022Article
- Chondroprotective effects of CDK4/6 inhibition via enhanced ubiquitin-dependent degradation of JUN in synovial fibroblasts.Rheumatology (Oxford, England) · 2022Article
- Cynarin attenuates LPS-induced endothelial inflammation via upregulation of the negative regulator MKP-3.Animal cells and systems · 2022Article
- Investigating the Mechanism of Inhibition of Cyclin-Dependent Kinase 6 Inhibitory Potential by Selonsertib: Newer Insights Into Drug Repurposing.Frontiers in oncology · 2022Article
- Article
- Inducible deletion of CDK4 and CDK6 - deciphering CDK4/6 inhibitor effects in the hematopoietic system.Haematologica · 2021Article
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nuclear factor kappa-B (NF-κB) activates multiple genes with overlapping roles in cell proliferation, inflammation and cancer. Using an unbiased approach we identified human CDK6 as a novel kinase phosphorylating NF-κB p65 at serine 536. Purified and reconstituted CDK6/cyclin complexes phosphorylated p65 in vitro and in transfected cells. The physiological role of CDK6 for basal as well as cytokine-induced p65 phosphorylation or NF-κB activation was revealed upon RNAi-mediated suppression of CDK6. Inhibition of CDK6 catalytic activity by PD332991 suppressed activation of NF-κB and TNF-induced gene expression. In complex with a constitutively active viral cyclin CDK6 stimulated NF-κB p65-mediated transcription in a target gene specific manner and this effect was partially dependent on its ability to phosphorylate p65 at serine 536. Tumor formation in thymi and spleens of v-cyclin transgenic mice correlated with increased levels of p65 Ser536 phosphorylation, increased expression of CDK6 and upregulaton of the NF-κB target cyclin D3. These results suggest that aberrant CDK6 expression or activation that is frequently observed in human tumors can contribute through NF-κB to chronic inflammation and neoplasia.
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