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Mol Cell. 2014 Jan 23;53(2):193-208. doi: 10.1016/j.molcel.2013.12.002. Epub 2014 Jan 2.

Cyclin-dependent kinase 6 is a chromatin-bound cofactor for NF-κB-dependent gene expression.

Author information

1
Rudolf-Buchheim-Institute of Pharmacology, Justus-Liebig-University Giessen, 35392 Giessen, Germany.
2
Institute for Genetics, Justus-Liebig-University Giessen, 35392 Giessen, Germany.
3
Institute of Physiological Chemistry, Medical School Hannover, 30625 Hannover, Germany.
4
Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
5
Institute of Biochemistry, Justus-Liebig-University Giessen, 35392 Giessen, Germany.
6
Rudolf-Buchheim-Institute of Pharmacology, Justus-Liebig-University Giessen, 35392 Giessen, Germany. Electronic address: michael.kracht@pharma.med.uni-giessen.de.

Erratum in

  • Mol Cell. 2014 Feb 20;53(4):682.

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.

PMID:
24389100
DOI:
10.1016/j.molcel.2013.12.002
[Indexed for MEDLINE]
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