ArticleNucleic acids research2023
CDK8 and CDK19: positive regulators of signal-induced transcription and negative regulators of Mediator complex proteins.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 64 citations in OpenAlex.
- CDK8/19 inhibition prevents adaptive resistance to CDK4/6 inhibitors in vitro and in vivo.Cell reports. Medicine · 2026Article
- Cyclins and Cyclin-Dependent Kinases: Structure, Biological Functions, and Innovative Targeting Strategies in Cancer.MedComm · 2026Review
- Article
- CDK8 Inhibition Releases the Muscle Differentiation Block in Fusion-driven Alveolar Rhabdomyosarcoma.Cancer discovery · 2026Article
- Review
- Cyclin C promotes pancreatic developmentand suppresses cancer initiation by maintenance of the autophagy-lysosome pathway.iScience · 2026Article
- The Mediator Complex: From Transcriptional Regulation to Disease Pathogenesis.International journal of molecular sciences · 2026Review
- Anoikis resistance and metastasis of ovarian cancer can be overcome by CDK8/19 mediator kinase inhibition.JCI insight · 2026Article
- NUDT21-mediated Alternative Polyadenylation of CDK19 Reprograms Cholesterol Biosynthesis to Drive Colorectal Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Inhibition of p38 MAPK after repetitive mTBI ameliorates immune signaling and functional deficits.Acta neuropathologica communications · 2026Article
- Inhibition of CDK8 rescues impaired ischemic fracture healing.NPJ Regenerative medicine · 2026Article
- Anti-tumor activity of valproic acid in EBV-positive Burkitt lymphoma via PFN2-associated PI3K/AKT pathway repression.Frontiers in pharmacology · 2026Article
- The Role of CDKs in the Regulation of the Monocyte/Macrophage Immune Response.Current medicinal chemistry · 2026Review
- Role of PBAF and Mediator kinase module in the RELA-dependent activation ofFrontiers in immunology · 2026Article
- CDK8 mediated inflammatory microenvironment aggravates osteoarthritis progression.Journal of advanced research · 2025Article
- Exploiting targeted degradation of cyclins and cyclin-dependent kinases for cancer therapeutics: a review.Journal of Zhejiang University. Science. B · 2025Review
- Cyclin dependent kinase 9 inhibitor induces transcription-replication conflicts and DNA damage accumulation in breast cancer.Cancer cell international · 2025Article
- Mediator Kinase Inhibitor Selectivity and Activity in Colorectal Cancer.ACS chemical biology · 2025Article
- Review
- Article
Corrections and comments
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Authors and funding
25 authors at 4 institutions in 3 countries.
Funding
Abstract
We have conducted a detailed transcriptomic, proteomic and phosphoproteomic analysis of CDK8 and its paralog CDK19, alternative enzymatic components of the kinase module associated with transcriptional Mediator complex and implicated in development and diseases. This analysis was performed using genetic modifications of CDK8 and CDK19, selective CDK8/19 small molecule kinase inhibitors and a potent CDK8/19 PROTAC degrader. CDK8/19 inhibition in cells exposed to serum or to agonists of NFκB or protein kinase C (PKC) reduced the induction of signal-responsive genes, indicating a pleiotropic role of Mediator kinases in signal-induced transcriptional reprogramming. CDK8/19 inhibition under basal conditions initially downregulated a small group of genes, most of which were inducible by serum or PKC stimulation. Prolonged CDK8/19 inhibition or mutagenesis upregulated a larger gene set, along with a post-transcriptional increase in the proteins comprising the core Mediator complex and its kinase module. Regulation of both RNA and protein expression required CDK8/19 kinase activities but both enzymes protected their binding partner cyclin C from proteolytic degradation in a kinase-independent manner. Analysis of isogenic cell populations expressing CDK8, CDK19 or their kinase-inactive mutants revealed that CDK8 and CDK19 have the same qualitative effects on protein phosphorylation and gene expression at the RNA and protein levels, whereas differential effects of CDK8 versus CDK19 knockouts were attributable to quantitative differences in their expression and activity rather than different functions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.