Institute of Biochemistry, Medical Faculty, Friedrichstrasse 24, Justus-Liebig-University, 35392 Giessen, Germany.
Rudolf-Buchheim-Institute for Pharmacology, Medical Faculty, Schubertstrasse 81, Justus-Liebig-University Giessen, 35392 Giessen, Germany.
Trends Pharmacol Sci. 2016 Feb;37(2):101-113. doi: 10.1016/j.tips.2015.10.004. Epub 2015 Dec 22.
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.
细胞周期蛋白依赖性激酶（CDKs）通过调节细胞周期和基因表达发挥多种功能，因此它们参与了多种生物过程。最近的研究揭示了核 CDK 用于支持炎症介质表达的分子机制。在细胞周期的 G1 期，许多促炎基因的诱导转录以 CDK 依赖性方式增加。这个过程涉及细胞因子诱导 CDK6 募集到核染色质部分，在那里它与 NF-κB、STAT 和 AP-1 家族的转录因子结合。CDK6 触发 VEGF-A 和 p16(INK4A) 的表达以及将 NF-κB 亚基 p65 招募到其靶位点的能力在很大程度上与其激酶功能无关。CDKs 参与促炎基因表达也允许针对其功能的治疗靶向，以干扰促进肿瘤的炎症或慢性炎症性疾病。
