ArticleMolecular and cellular biology2010
Cyclin-dependent kinase 8 positively cooperates with Mediator to promote thyroid hormone receptor-dependent transcriptional activation.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 65 citations in OpenAlex.
- Targeting Transcriptional Cyclin-Dependent Kinases in Cancer.Molecular cancer therapeutics · 2025Review
- Targeting CDKs in cancer therapy: advances in PROTACs and molecular glues.NPJ precision oncology · 2025Review
- An IDR-dependent mechanism for nuclear receptor control of Mediator interaction with RNA polymerase II.Molecular cell · 2024Article
- Discovery of small molecule degraders for modulating cell cycle.Frontiers of medicine · 2023Review
- Elongin functions as a loading factor for Mediator at ATF6α-regulated ER stress response genes.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Stress-Induced Cyclin C Translocation Regulates Cardiac Mitochondrial Dynamics.Journal of the American Heart Association · 2020Article
- Mediator subunit MED1 modulates intranuclear dynamics of the thyroid hormone receptor.Journal of cellular biochemistry · 2020Article
- Targeting transcriptional machinery to inhibit enhancer-driven gene expression in heart failure.Heart failure reviews · 2019Review
- Cell cycle regulation and hematologic malignancies.Blood science (Baltimore, Md.) · 2019Review
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- Control of Muscle Metabolism by the Mediator Complex.Cold Spring Harbor perspectives in medicine · 2018Review
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- Inhibition of CDK8 mediator kinase suppresses estrogen dependent transcription and the growth of estrogen receptor positive breast cancer.Oncotarget · 2017Article
- Mediator Undergoes a Compositional Change during Transcriptional Activation.Molecular cell · 2016Article
- Dual role of Med12 in PRC1-dependent gene repression and ncRNA-mediated transcriptional activation.Cell cycle (Georgetown, Tex.) · 2016Article
- A MED13-dependent skeletal muscle gene program controls systemic glucose homeostasis and hepatic metabolism.Genes & development · 2016Article
- The RNAPII-CTD Maintains Genome Integrity through Inhibition of Retrotransposon Gene Expression and Transposition.PLoS genetics · 2015Article
- MicroRNA-101 is a potential prognostic indicator of laryngeal squamous cell carcinoma and modulates CDK8.Journal of translational medicine · 2015Article
- Retroviral cyclin controls cyclin-dependent kinase 8-mediated transcription elongation and reinitiation.Journal of virology · 2015Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Mediator is a multisubunit assemblage of proteins originally identified in humans as a coactivator bound to thyroid hormone receptors (TRs) and essential for thyroid hormone (T3)-dependent transcription. Cyclin-dependent kinase 8 (CDK8), cyclin C, MED12, and MED13 form a variably associated Mediator subcomplex (termed the CDK8 module) whose functional role in TR-dependent transcription remains unclear. Using in vitro and cellular approaches, we show here that Mediator complexes containing the CDK8 module are specifically recruited into preinitiation complexes at the TR target gene type I deiodinase (DioI) together with RNA polymerase II (Pol II) in a TR- and T3-dependent manner. We found that CDK8 is essential for robust T3-dependent Dio1 transcription and that CDK8 knockdown via RNA interference decreased Pol II occupancy, and also the recruitment of the Pol II kinase CDK9, at the DioI promoter. Chromatin immunoprecipitation revealed CDK8 occupancy at the DioI promoter concurrent with active transcription, thus suggesting CDK8 involvement in transcriptional reinitiation. Mutagenesis assays showed that CDK8 kinase activity is necessary for full T3-dependent DioI activation, whereas in vitro kinase studies indicated that CDK8 may contribute to Pol II phosphorylation. Collectively, our data suggest CDK8 plays an important coactivator role in TR-dependent transcription by promoting Pol II recruitment and activation at TR target gene promoters.
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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.