ArticleNature chemical biology2017
Small-molecule studies identify CDK8 as a regulator of IL-10 in myeloid cells.
Article in Nature chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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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
37 citing papers in PubMed, 68 citations in OpenAlex.
- Discovery of CDK8/19 inhibitors as lead compounds for IL-6-dependent lymphoma enabled by the formal synthesis of cortistatin A.Science advances · 2026Article
- A novel CDK8/19 inhibitor RO8323 mitigates allograft rejection through dual mechanisms of action to modulate regulatory T cell and myeloid cell.Acta pharmacologica Sinica · 2026Article
- Review
- Article
- The Role of CDKs in the Regulation of the Monocyte/Macrophage Immune Response.Current medicinal chemistry · 2026Review
- Submicron-Sampling of Living Cells by Macrophages.bioRxiv : the preprint server for biology · 2025Article
- Lyn expression in macrophages promotes TLR activation and restricts proliferation in an isoform-independent manner.Journal of leukocyte biology · 2025Article
- CDK8 mediated inflammatory microenvironment aggravates osteoarthritis progression.Journal of advanced research · 2025Article
- Mediator Kinase Inhibitor Selectivity and Activity in Colorectal Cancer.ACS chemical biology · 2025Article
- Mediator kinase inhibition suppresses hyperactive interferon signaling in Down syndrome.eLife · 2025Article
- Microglia depletion reduces human neuronal APOE4-related pathologies in a chimeric Alzheimer's disease model.Cell stem cell · 2025Article
- Discovery of lipid metabolism-related diagnostic biomarkers and construction of diagnostic model in steroid-induced osteonecrosis of femoral head.Open medicine (Warsaw, Poland) · 2025Article
- Mediator kinase inhibition suppresses hyperactive interferon signaling in Down syndrome.bioRxiv : the preprint server for biology · 2024Article
- Small molecule inhibitors of transcriptional cyclin-dependent kinases impose HIV-1 latency, presenting "block and lock" treatment strategies.Antimicrobial agents and chemotherapy · 2024Article
- Unveiling the impact of CDK8 on tumor progression: mechanisms and therapeutic strategies.Frontiers in pharmacology · 2024Review
- CDK8 inhibitors antagonize HIV-1 reactivation and promote provirus latency in T cells.Journal of virology · 2023Article
- Article
- The E3 ligase TRIM31 regulates hematopoietic stem cell homeostasis and MLL-AF9 leukemia.Haematologica · 2023Article
- CDK8 and CDK19 act redundantly to control the CFTR pathway in the intestinal epithelium.EMBO reports · 2023Article
- The Mediator kinase module: an interface between cell signaling and transcription.Trends in biochemical sciences · 2022Review
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 1 country.
Funding
Abstract
Enhancing production of the anti-inflammatory cytokine interleukin-10 (IL-10) is a promising strategy to suppress pathogenic inflammation. To identify new mechanisms regulating IL-10 production, we conducted a phenotypic screen for small molecules that enhance IL-10 secretion from activated dendritic cells. Mechanism-of-action studies using a prioritized hit from the screen, BRD6989, identified the Mediator-associated kinase CDK8, and its paralog CDK19, as negative regulators of IL-10 production during innate immune activation. The ability of BRD6989 to upregulate IL-10 is recapitulated by multiple, structurally differentiated CDK8 and CDK19 inhibitors and requires an intact cyclin C-CDK8 complex. Using a highly parallel pathway reporter assay, we identified a role for enhanced AP-1 activity in IL-10 potentiation following CDK8 and CDK19 inhibition, an effect associated with reduced phosphorylation of a negative regulatory site on c-Jun. These findings identify a function for CDK8 and CDK19 in regulating innate immune activation and suggest that these kinases may warrant consideration as therapeutic targets for inflammatory disorders.
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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.