ArticleGenes & development2009
The human CDK8 subcomplex is a molecular switch that controls Mediator coactivator function.
Article in Genes & development, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 217 papers.
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Who cites it
217 citing papers in PubMed.
- The Mediator complex: co-transcriptional regulation and beyond.RNA biology · 2026Review
- MED26 facilitates Mediator-Pol II complex assembly and promotes nuclear stress body formation during heat stress.iScience · 2026Article
- The Role of Transcriptional and Atypical Cyclin-Dependent Protein Kinases in Melanoma.Cancers · 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
- Maternal Med12 safeguards trophoblast pluripotency and placental development.Biology of reproduction · 2026Article
- Molecular pathology of phyllodes tumours of the breast-much more than MED12.Histopathology · 2026Review
- Med14 phosphorylation shapes genomic response to GLP-1 agonists.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A tryptophan-phenylalanine binding motif for the histone methyltransferases MLL4 and MLL3.The Journal of biological chemistry · 2026Article
- The Mediator Complex: From Transcriptional Regulation to Disease Pathogenesis.International journal of molecular sciences · 2026Review
- 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
- Genetic, Clinical and Neuroradiological Spectrum of MED-Related Disorders: An Updated Review.Genes · 2025Review
- UTERINE FIBROIDS.Physiological reviews · 2025Review
- The Mediator Complex: A Regulatory Hub for Transcriptional Activity of Nuclear Receptors.Cells · 2025Review
- Regulation of cortical neurogenesis by MED13L via transcriptional priming and its implications for MED13L syndrome.Communications biology · 2025Article
- Epigenetic regulation of MED12: a key contributor to the leukemic chromatin landscape and transcriptional dysregulation.Epigenetics & chromatin · 2025Article
- Mechanistic Roles of Transcriptional Cyclin-Dependent Kinases in Oncogenesis: Implications for Cancer Therapy.Cancers · 2025Review
- Bi-allelic MED16 variants cause a MEDopathy with intellectual disability, motor delay, and craniofacial, cardiac, and limb malformations.American journal of human genetics · 2025Article
- A novel frameshift variant in theFrontiers in pediatrics · 2025Article
157 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
The human CDK8 subcomplex (CDK8, cyclin C, Med12, and Med13) negatively regulates transcription in ways not completely defined; past studies suggested CDK8 kinase activity was required for its repressive function. Using a reconstituted transcription system together with recombinant or endogenous CDK8 subcomplexes, we demonstrate that, in fact, Med12 and Med13 are critical for subcomplex-dependent repression, whereas CDK8 kinase activity is not. A hallmark of activated transcription is efficient reinitiation from promoter-bound scaffold complexes that recruit a series of pol II enzymes to the gene. Notably, the CDK8 submodule strongly represses even reinitiation events, suggesting a means to fine tune transcript levels. Structural and biochemical studies confirm the CDK8 submodule binds the Mediator leg/tail domain via the Med13 subunit, and this submodule-Mediator association precludes pol II recruitment. Collectively, these results reveal the CDK8 subcomplex functions as a simple switch that controls the Mediator-pol II interaction to help regulate transcription initiation and reinitiation events. As Mediator is generally required for expression of protein-coding genes, this may reflect a common mechanism by which activated transcription is shut down in human cells.
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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.