ArticleThe Journal of biological chemistry
The Cdk8 kinase module regulates interaction of the mediator complex with RNA polymerase II.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 75 citations in OpenAlex.
- RNA polymerase II phosphorylation dynamics: from molecular mechanisms to human disease.RNA biology · 2026Review
- CDK8 phosphorylation of DELLA limits Mediator recruitment in gibberellin signaling.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Non-canonical subunit functions in multiprotein complexes: insights from the Mediator complex.Biochemical Society transactions · 2026Review
- CDK8 phosphorylation of DELLA limits Mediator recruitment in gibberellin signaling.bioRxiv : the preprint server for biology · 2026Article
- Anoikis resistance and metastasis of ovarian cancer can be overcome by CDK8/19 mediator kinase inhibition.JCI insight · 2026Article
- Inhibition of CDK8 rescues impaired ischemic fracture healing.NPJ Regenerative medicine · 2026Article
- Genetic, Clinical and Neuroradiological Spectrum of MED-Related Disorders: An Updated Review.Genes · 2025Review
- Differential regulation during development, aging, and disease implies heart cell specific functions of the Mediator Complex.Journal of molecular and cellular cardiology plus · 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
- Review
- Article
- CDK8/19 inhibition attenuates G1 arrest induced by BCR-ABL antagonists and accelerates death of chronic myelogenous leukemia cells.Cell death discovery · 2025Article
- Remembering foods and foes: emerging principles of transcriptional memory.Cell death and differentiation · 2025Review
- The CDK8 kinase module: A novel player in the transcription of translation initiation and ribosomal genes.Molecular biology of the cell · 2025Article
- Distinct effects of CDK8 module subunits on cellular growth and proliferation in Drosophila.Development (Cambridge, England) · 2024Article
- Mediator kinase inhibitors suppress triple-negative breast cancer growth and extend tumor suppression by mTOR and AKT inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Structural basis of the human transcriptional Mediator regulated by its dissociable kinase module.Molecular cell · 2024Article
- Novel insights into the phenotypic spectrum and pathogenesis of Hardikar syndrome.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Structures and compositional dynamics of Mediator in transcription regulation.Current opinion in structural biology · 2024Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Cdk8 kinase module (CKM) is a dissociable part of the coactivator complex mediator, which regulates gene transcription by RNA polymerase II. The CKM has both negative and positive functions in gene transcription that remain poorly understood at the mechanistic level. In order to reconstitute the role of the CKM in transcription initiation, we prepared recombinant CKM from the yeast Saccharomyces cerevisiae. We showed that CKM bound to the core mediator (cMed) complex, sterically inhibiting cMed from binding to the polymerase II preinitiation complex (PIC) in vitro. We further showed that the Cdk8 kinase activity of the CKM weakened CKM-cMed interaction, thereby facilitating dissociation of the CKM and enabling mediator to bind the PIC in order to stimulate transcription initiation. Finally, we report that the kinase activity of Cdk8 is required for gene activation during the stressful condition of heat shock in vivo but not under steady-state growth conditions. Based on these results, we propose a model in which the CKM negatively regulates mediator function at upstream-activating sequences by preventing mediator binding to the PIC at the gene promoter. However, during gene activation in response to stress, the Cdk8 kinase activity of the CKM may release mediator and allow its binding to the PIC, thereby accounting for the positive function of CKM. This may impart improved adaptability to stress by allowing a rapid transcriptional response to environmental changes, and we speculate that a similar mechanism in metazoans may allow the precise timing of developmental transcription programs.
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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.