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CDK8/19 Mediator kinases potentiate induction of transcription by NF kappa B 期刊论文

编号：

5ff644b1-0768-4089-905d-72d3358f13ef
作者：

Chen, Mengqian#^[1]Liang, Jiaxin^[1];Ji, Hao^[1];Yang, Zhengguan^[1];Altilia, Serena^[1];Hu, Bing(胡兵)^[1,2]Schronce, Adam^[1];McDermott, Martina S. J.^[1];Schools, Gary P.^[1];Lim, Changuk^[1];Oliver, David^[1];Shtutman, Michael S.^[1];Lu, Tao^[3];Stark, George R.*^[4]Porter, Donald C.^[5];Broude, Eugenia V.^[1];Roninson, Igor B.*^[1]
语种：

英文
期刊：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA ISSN：0027-8424 2017 年 114 卷 38 期 (10208 - 10213) ; SEP 19
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关键词：

NF kappa B CDK8 CDK19 RNA polymerase II regulation of transcription
摘要：

The nuclear factor-kappa B (NF kappa B) family of transcription factors has been implicated in inflammatory disorders, viral infections, and cancer. Most of the drugs that inhibit NF kappa B show significant side effects, possibly due to sustained NF kappa B suppression. Drugs affecting induced, but not basal, NF kappa B activity may have the potential to provide therapeutic benefit without associated toxicity. NF kappa B activation by stress-inducible cell cycle inhibitor p21 was shown to be mediated by a p21-stimulated transcription-regulating kinase CDK8. CDK8 and its paralog CDK19, associated with the transcriptional Mediator complex, act as coregulators of several transcription factors implicated in cancer; CDK8/19 inhibitors are entering clinical development. Here we show that CDK8/19 inhibition by different small-molecule kinase inhibitors or shRNAs suppresses the elongation of NF kappa B-induced transcription when such transcription is activated by p21-independent canonical inducers, such as TNF alpha. On NF kappa B activation, CDK8/19 are corecruited with NF kappa B to the promoters of the responsive genes. Inhibition of CDK8/19 kinase activity suppresses the RNA polymerase II C-terminal domain phosphorylation required for transcriptional elongation, in a gene-specific manner. Genes coregulated by CDK8/19 and NF kappa B include IL8, CXCL1, and CXCL2, which encode tumor-promoting proinflammatory cytokines. Although it suppressed newly induced NF kappa B-driven transcription, CDK8/19 inhibition in most cases had no effect on the basal expression of NF kappa B-regulated genes or promoters; the same selective regulation of newly induced transcription was observed with other transcription signals potentiated by CDK8/19. This selective role of CDK8/19 identifies these kinases as mediators of transcriptional reprogramming, a key aspect of development and differentiation as well as pathological processes.
推荐引用方式
GB/T 7714：

Chen Mengqian,Liang Jiaxin,Ji Hao, et al. CDK8/19 Mediator kinases potentiate induction of transcription by NF kappa B [J].PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2017,114(38):10208-10213.
APA：

Chen Mengqian,Liang Jiaxin,Ji Hao,Yang Zhengguan,&Roninson Igor B..(2017).CDK8/19 Mediator kinases potentiate induction of transcription by NF kappa B .PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,114(38):10208-10213.
MLA：

Chen Mengqian, et al. "CDK8/19 Mediator kinases potentiate induction of transcription by NF kappa B" .PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 114,38(2017):10208-10213.
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