ArticleNature structural & molecular biology2013
A conserved Mediator-CDK8 kinase module association regulates Mediator-RNA polymerase II interaction.
Article in Nature structural & molecular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers.
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Who cites it
143 citing papers in PubMed.
- RNA polymerase II phosphorylation dynamics: from molecular mechanisms to human disease.RNA biology · 2026Review
- Regulation of RNA transcript elongation in metazoans and its relevance to disease.Nature reviews. Molecular cell biology · 2026Review
- CDK8 Inhibition Releases the Muscle Differentiation Block in Fusion-driven Alveolar Rhabdomyosarcoma.Cancer discovery · 2026Article
- Non-canonical subunit functions in multiprotein complexes: insights from the Mediator complex.Biochemical Society transactions · 2026Review
- Genetic and environmental determinants of multicellular-like phenotypes in fission yeast.Genetics · 2026Article
- CDK8 Inhibition Increases E2F1 Transcriptional Activity and Promotes STAT3-Dependent Suppression of Mcl-1 in Triple-Negative Breast Cancer Cell Line MDA-MB-468.International journal of molecular sciences · 2026Article
- 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
- Structural and evolutionary determinants of Argonaute function.Nucleic acids research · 2025Article
- Regulation of cortical neurogenesis by MED13L via transcriptional priming and its implications for MED13L syndrome.Communications biology · 2025Article
- MED12 dysregulation: insights into cancer and therapeutic resistance.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- The indispensable role of Mediator complex subunit 27 during neurodevelopment.Cell & bioscience · 2025Article
- The Mediator Kinase Module regulates cell cycle re-entry and transcriptional responses following DNA damage.bioRxiv : the preprint server for biology · 2025Article
- Mechanistic Roles of Transcriptional Cyclin-Dependent Kinases in Oncogenesis: Implications for Cancer Therapy.Cancers · 2025Review
- Cyclin-dependent kinases as mediators of aberrant transcription in prostate cancer.Translational oncology · 2025Review
- Review
- A Protocol to Purify Human Mediator Complex From Freestyle 293-F Cells.Bio-protocol · 2025Article
- The CDK8 kinase module: A novel player in the transcription of translation initiation and ribosomal genes.Molecular biology of the cell · 2025Article
- A novel frameshift variant in theFrontiers in pediatrics · 2025Article
- Distinct effects of CDK8 module subunits on cellular growth and proliferation in Drosophila.Development (Cambridge, England) · 2024Article
83 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
Funding
Abstract
The CDK8 kinase module (CKM) is a conserved, dissociable Mediator subcomplex whose component subunits were genetically linked to the RNA polymerase II (RNAPII) C-terminal domain (CTD) and individually recognized as transcriptional repressors before Mediator was identified as a pre-eminent complex in eukaryotic transcription regulation. We used macromolecular EM and biochemistry to investigate the subunit organization, structure and Mediator interaction of the Saccharomyces cerevisiae CKM. We found that interaction of the CKM with Mediator's middle module interferes with CTD-dependent RNAPII binding to a previously unknown middle-module CTD-binding site and with the holoenzyme formation process. Taken together, our results reveal the basis for CKM repression, clarify the origin of the connection between CKM subunits and the CTD and suggest that a combination of competitive interactions and conformational changes that facilitate holoenzyme formation underlie the mechanism of transcription regulation by Mediator.
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