Cyclin-Dependent Kinases as Coregulators of Inflammatory Gene Expression

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• 作者：M. Lienhard Schmitz¹ ; ^{lienhard.schmitz@biochemie.med.unic-giessen.de" class="auth_mail" title="E-mail the corresponding author} ; Michael Kracht² ; ^{michael.kracht@pharma.med.uni-giessen.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：cyclin-dependent kinases ; inflammation ; cell cycle ; NF-κB ; cancer
• 刊名：Trends in Pharmacological Sciences
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：37
• 期：2
• 页码：101-113
• 全文大小：2092 K

文摘

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.