title: Cyclin-Dependent Kinases as Coregulators of Inflammatory Gene Expression.
abstract: Cyclin-dependent kinases (CDKs) exert a variety of functions through regulation of the cell cycle and gene expression, thus implicating them in diverse biological processes. Recent studies have deciphered the molecular mechanisms employed by nuclear CDKs to support the expression of inflammatory mediators. Induced transcription of many proinflammatory genes is increased during the G1 phase of the cell cycle in a CDK-dependent manner. This process involves the cytokine-induced recruitment of CDK6 to the nuclear chromatin fraction where it associates with transcription factors of the NF-κB, STAT, and AP-1 families. The ability of CDK6 to trigger the expression of VEGF-A and p16(INK4A) and to recruit the NF-κB subunit p65 to its target sites is largely independent of its kinase function. The involvement of CDKs in proinflammatory gene expression also allows therapeutic targeting of their functions to interfere with tumor-promoting inflammation or chronic inflammatory diseases.
authors.affiliation: Institute of Biochemistry, Medical Faculty, Friedrichstrasse 24, Justus-Liebig-University, 35392 Giessen, Germany. Electronic address: lienhard.schmitz@biochemie.med.unic-giessen.de.
authors.forename: M Lienhard
authors.initials: ML
authors.lastname: Schmitz
authors.affiliation: Rudolf-Buchheim-Institute for Pharmacology, Medical Faculty, Schubertstrasse 81, Justus-Liebig-University Giessen, 35392 Giessen, Germany. Electronic address: michael.kracht@pharma.med.uni-giessen.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Kracht
mesh_terms: D000818:Animals; D018844:Cyclin-Dependent Kinases / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology
chemical_list: D018844:Cyclin-Dependent Kinases
keywords: NF-κB; cancer; cell cycle; cyclin-dependent kinases; inflammation