CDK8/19 Mediator kinases potentiate induction of transcription by NFκB
Abstract
Nuclear factor-κB (NFκB) transcription factors have been implicated in several major diseases, including inflammatory disorders, viral infections, and cancer. NFκB-inhibiting drugs typically have side effects, possibly due to sustained NFκB suppression. The ability to affect induced, but not basal, NFκB activity could provide therapeutic benefit without associated toxicity. We report that the transcription-regulating kinases CDK8/19 potentiate NFκB activity, including the expression of tumor-promoting proinflammatory cytokines, by enabling the completion of NFκB-initiated transcription. CDK8/19 inhibitors suppress the induction of gene expression by NFκB or other transcription factors, but generally do not affect basal expression of the same genes. The role of CDK8/19 in newly induced transcription identifies these kinases as mediators of transcriptional reprogramming, a key aspect of development, differentiation, and pathological processes.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 30, 2017
- Source ID
- 10.1073/pnas.1710467114
Entities
People
- Adam Schronce
- Bing Hu
- Chang-uk Lim
- David Oliver
- Donald C. Porter
- Eugenia V. Broude
- Gary P. Schools
- George R Stark
- Hao Ji
- Igor B Roninson
- Jiaxin Liang
- Martina S. J. Mcdermott
- Mengqian Chen
- Michael Shtutman
- Serena Altilia
- Tao Lu
- Zhengguan Yang
Organizations
- American Cancer Society
- Cleveland Clinic
- Indiana University School of Medicine
- National Institutes of Health
- Shanghai University of Traditional Chinese Medicine
- Susan G. Komen for the Cure
- United States Department of Defense
- University of South Carolina