Cited by 141NF-κB Signaling PathwaysSignaling Pathways in DiseaseGenomics and Chromatin Dynamics

Cyclin-Dependent Kinase 6 Is a Chromatin-Bound Cofactor for NF-κB-Dependent Gene Expression

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Handschick, Katja, Beuerlein, Knut, Jurida, Liane, Bartkuhn, Marek, Müller, Helmut, Soelch, Johanna, Weber, Axel, Dittrich-Breiholz, Oliver +6 more·2014·Molecular Cell

Abstract

Given the intimate link between inflammation and dysregulated cell proliferation in cancer, we investigated cytokine-triggered gene expression in different cell cycle stages. Transcriptome analysis revealed that G1 release through cyclin-dependent kinase 6 (CDK6) and CDK4 primes and cooperates with the cytokine-driven gene response. CDK6 physically and functionally interacts with the NF-κB subunit p65 in the nucleus and is found at promoters of many transcriptionally active NF-κB target genes. CDK6 recruitment to distinct chromatin regions of inflammatory genes was essential for proper loading of p65 to its cognate binding sites and for the function of p65 coactivators, such as TRIP6. Furthermore, cytokine-inducible nuclear translocation and chromatin association of CDK6 depends on the kinase activity of TAK1 and p38. These results have widespread biological implications, as aberrant CDK6 expression or activation that is frequently observed in human tumors modulates NF-κB to shape the cytokine and chemokine repertoires in chronic inflammation and cancer.

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Crossref · 10.1016/j.molcel.2013.12.002

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Authors
Handschick, K., Beuerlein, K., Jurida, L., Bartkuhn, M., Müller, H., Soelch, J., Weber, A., Dittrich-Breiholz, O., Schneider, H., Scharfe, M., Jarek, M., Stellzig, J., Schmitz, M. L., & Kracht, M.
Affiliations
  • Justus-Liebig-Universität Gießen (DE)
  • Medizinische Hochschule Hannover (DE)
  • Helmholtz Centre for Infection Research (DE)
Corresponding author
Kracht, Michael
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2014-01
Volume
53
Issue
2
Pages
193-208
ISSN
1097-2765 (ISSN-L)
OpenAlex
W2016098919
Cited by
141
References
47
Citations by year
2026: 7 · 2025: 6 · 2024: 4 · 2023: 10 · 2022: 15 · 2021: 12 · 2020: 15 · 2019: 18 · 2018: 11 · 2017: 9 · 2016: 15 · 2015: 12 · 2014: 7
FWCI
4.59
Type
journal article
Language
en
Update notices
erratum (2014-02-20)
Open access
Locations
  • Molecular Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
Deutsche Forschungsgemeinschaft
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
CDK6, NF-κB, NF-κB p65, cytokine-induced gene expression, CDK4, TRIP6, p38 MAPK, TAK1, nuclear translocation, chronic inflammation, cancer, chemokines, transcriptional regulation
MeSH terms
MAP Kinase Kinase Kinase 7, Cell Cycle, Chromatin, Gene Expression Regulation, HeLa Cells, Humans, Interleukin-1, Promoter Regions, Genetic, Tumor Necrosis Factor-alpha, Interleukin-8, NF-kappa B, MAP Kinase Kinase Kinases, p38 Mitogen-Activated Protein Kinases, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6, Transcription Factor RelA

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