The DOI matches its Crossref record; 51 of the 53 references it cites were found in a registry or an index.
CDK8 Kinase Phosphorylates Transcription Factor STAT1 to Selectively Regulate the Interferon Response
Open accessAbstract
Gene regulation by cytokine-activated transcription factors of the signal transducer and activator of transcription (STAT) family requires serine phosphorylation within the transactivation domain (TAD). STAT1 and STAT3 TAD phosphorylation occurs upon promoter binding by an unknown kinase. Here, we show that the cyclin-dependent kinase 8 (CDK8) module of the Mediator complex phosphorylated regulatory sites within the TADs of STAT1, STAT3, and STAT5, including S727 within the STAT1 TAD in the interferon (IFN) signaling pathway. We also observed a CDK8 requirement for IFN-γ-inducible antiviral responses. Microarray analyses revealed that CDK8-mediated STAT1 phosphorylation positively or negatively regulated over 40% of IFN-γ-responsive genes, and RNA polymerase II occupancy correlated with gene expression changes. This divergent regulation occurred despite similar CDK8 occupancy at both S727 phosphorylation-dependent and -independent genes. These data identify CDK8 as a key regulator of STAT1 and antiviral responses and suggest a general role for CDK8 in STAT-mediated transcription. As such, CDK8 represents a promising target for therapeutic manipulation of cytokine responses.
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“In macrophages, CDK8 appears to be the main kinase driving STAT1 serine phosphorylation in response to IFN gamma stimulation”
From CDK8 fine-tunes IL-6 transcriptional activities by limiting STAT3 resident time at the gene loci (2020) · cites this paper as Bancerek et al., 2013
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“Previous studies have described CDKs as regulators of STAT1 Ser phosphorylation in different systems”
From CDK8 fine-tunes IL-6 transcriptional activities by limiting STAT3 resident time at the gene loci (2020) · cites this paper as Bancerek et al., 2013
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Citations
Cites
STATs: transcriptional control and biological impact
Levy, D. E., & Darnell, J. E. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm909 · Cited by 3,201
Todaro, G. J., & Green, H. (1963) · The Journal of Cell Biology · doi:10.1083/jcb.17.2.299 · Cited by 2,747
Wen, Z., Zhong, Z., & Darnell, J. E. (1995) · Cell · doi:10.1016/0092-8674(95)90311-9 · Cited by 1,974
Mediator and cohesin connect gene expression and chromatin architecture
Kagey, M. H., Newman, J. J., Bilodeau, S., Zhan, Y., Orlando, D. A., van Berkum, N. L., Ebmeier, C. C., Goossens, J., Rahl, P. B., Levine, S. S., et al. (2010) · Nature · doi:10.1038/nature09380 · Cited by 1,939
Self-citationTargeted Disruption of the Mouse Stat1 Gene Results in Compromised Innate Immunity to Viral Disease
Durbin, J. E., Hackenmiller, R., Simon, M. C., & Levy, D. E. (1996) · Cell · doi:10.1016/s0092-8674(00)81289-1 · Cited by 1,539
Serine phosphorylation of STATs
Decker, T., & Kovarik, P. (2000) · Oncogene · doi:10.1038/sj.onc.1203481 · Cited by 887
Self-citationNuclear CDKs Drive Smad Transcriptional Activation and Turnover in BMP and TGF-β Pathways
Alarcón, C., Zaromytidou, A.-I., Xi, Q., Gao, S., Yu, J., Fujisawa, S., Barlas, A., Miller, A. N., Manova-Todorova, K., Macias, M. J., et al. (2009) · Cell · doi:10.1016/j.cell.2009.09.035 · Cited by 719
CDK8 is a colorectal cancer oncogene that regulates β-catenin activity
Firestein, R., Bass, A. J., Kim, S. Y., Dunn, I. F., Silver, S. J., Guney, I., Freed, E., Ligon, A. H., Vena, N., Ogino, S., et al. (2008) · Nature · doi:10.1038/nature07179 · Cited by 692
Immune Control of Tuberculosis by IFN-γ-Inducible LRG-47
MacMicking, J. D., Taylor, G. A., & McKinney, J. D. (2003) · Science · doi:10.1126/science.1088063 · Cited by 685 · cited 1×
“Primary Irf1, Wars (also known as Ifp-53), and Ifi47 are each regulated by binding of the STAT1 homodimer to the IFN-g-activated sequence (GAS) in the promoter (MacMicking et al., 2003; Pine et al., 1994; Strehlow et al., 1993).”
Mastermind Recruits CycC:CDK8 to Phosphorylate the Notch ICD and Coordinate Activation with Turnover
Fryer, C. J., White, B., & Jones, K. A. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.10.014 · Cited by 627
Flagged first, then by citations
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Cited by
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Regulation of type I interferon responses
Ivashkiv, L. B., & Donlin, L. T. (2013) · Nature reviews. Immunology · doi:10.1038/nri3581 · Cited by 3,442
IFNγ: signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy
Ivashkiv, L. B. (2018) · Nature reviews. Immunology · doi:10.1038/s41577-018-0029-z · Cited by 1,418
Mechanisms and consequences of Jak–STAT signaling in the immune system
Villarino, A. V., Kanno, Y., & O'Shea, J. J. (2017) · Nature Immunology · doi:10.1038/ni.3691 · Cited by 1,221
The Mediator complex: a central integrator of transcription
Allen, B. L., & Taatjes, D. J. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3951 · Cited by 922
Self-citationMechanisms of Jak/STAT Signaling in Immunity and Disease
Villarino, A. V., Kanno, Y., Ferdinand, J. R., & O’Shea, J. J. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401867 · Cited by 564
Metadata
- Authors
- Bancerek, J., Poss, Z. C., Steinparzer, I., Sedlyarov, V., Pfaffenwimmer, T., Mikulic, I., Dölken, L., Strobl, B., Müller, M., Taatjes, D. J., & Kovarik, P.
- Affiliations
- University of Vienna (AT)
- University of Colorado Boulder (US)
- University of Cambridge (GB)
- University of Veterinary Medicine Vienna (AT)
- Corresponding author
- Kovarik, Pavel
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 38
- Issue
- 2
- Pages
- 250-262
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC3580287
- OpenAlex
- W2059553622
- Cited by
- 297
- References
- 53
- Citations by year
- 2026: 32 · 2025: 28 · 2024: 29 · 2023: 21 · 2022: 23 · 2021: 20 · 2020: 24 · 2019: 27 · 2018: 19 · 2017: 24 · 2016: 15 · 2015: 13 · 2014: 13 · 2013: 9
- FWCI
- 8.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Immunity (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Austrian Science Fund
- Universität Wien
- National Institutes of Health
- National Cancer Institute (R01CA127364, P30CA046934)
- National Institute of General Medical Sciences (T32-GM08759, T32GM008759, T32GM142607)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- CDK8, STAT1, STAT3, STAT5, serine phosphorylation, transactivation domain, Mediator complex, interferon signaling, interferon-gamma, antiviral response, RNA polymerase II occupancy, gene expression regulation
- MeSH terms
- Animals, Fibroblasts, Gene Expression Regulation, Humans, Interferon-gamma, Phosphorylation, Promoter Regions, Genetic, RNA Polymerase II, Transcription, Genetic, Signal Transduction, Interleukin-6, Vesiculovirus, Oligonucleotide Array Sequence Analysis, STAT1 Transcription Factor, STAT3 Transcription Factor, STAT5 Transcription Factor, Mice, Cyclin-Dependent Kinase 8, Hep G2 Cells
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