ArticleProceedings of the National Academy of Sciences of the United States of America2014
Suppression of Mediator is regulated by Cdk8-dependent Grr1 turnover of the Med3 coactivator.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
32 citing papers in PubMed, 44 citations in OpenAlex.
- Review
- CRSP8-driven fatty acid metabolism reprogramming enhances hepatocellular carcinoma progression by inhibiting RAN-mediated PPARα nucleus-cytoplasm shuttling.Journal of experimental & clinical cancer research : CR · 2025Article
- The CDK8 kinase module: A novel player in the transcription of translation initiation and ribosomal genes.Molecular biology of the cell · 2025Article
- In silico enhancer mining reveals SNS-032 and EHMT2 inhibitors as therapeutic candidates in high-grade serous ovarian cancer.British journal of cancer · 2023Article
- Genetically Engineered Mice Unveil In Vivo Roles of the Mediator Complex.International journal of molecular sciences · 2023Review
- Article
- Article
- Cdk8 Kinase Module: A Mediator of Life and Death Decisions in Times of Stress.Microorganisms · 2021Review
- Connection of core and tail Mediator modules restrains transcription from TFIID-dependent promoters.PLoS genetics · 2021Article
- CRSP8 promotes thyroid cancer progression by antagonizing IKKα-induced cell differentiation.Cell death and differentiation · 2021Article
- Global hyperactivation of enhancers stabilizes human and mouse naive pluripotency through inhibition of CDK8/19 Mediator kinases.Nature cell biology · 2020Article
- Gene Transcription as a Limiting Factor in Protein Production and Cell Growth.G3 (Bethesda, Md.) · 2020Article
- Transcriptome Analysis of FourG3 (Bethesda, Md.) · 2018Article
- Candida glabrata Med3 Plays a Role in Altering Cell Size and Budding Index To Coordinate Cell Growth.Applied and environmental microbiology · 2018Article
- Snf1 cooperates with the CWI MAPK pathway to mediate the degradation of Med13 following oxidative stress.Microbial cell (Graz, Austria) · 2018Article
- Transcription regulation by the Mediator complex.Nature reviews. Molecular cell biology · 2018Review
- A complex molecular switch directs stress-induced cyclin C nuclear release through SCFMolecular biology of the cell · 2018Article
- Candida albicans Swi/Snf and Mediator Complexes Differentially Regulate Mrr1-InducedAntimicrobial agents and chemotherapy · 2017Article
- Mediator Tail Module Is Required for Tac1-ActivatedAntimicrobial agents and chemotherapy · 2017Article
- Article
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
Abstract
Mediator, an evolutionary conserved large multisubunit protein complex with a central role in regulating RNA polymerase II-transcribed genes, serves as a molecular switchboard at the interface between DNA binding transcription factors and the general transcription machinery. Mediator subunits include the Cdk8 module, which has both positive and negative effects on activator-dependent transcription through the activity of the cyclin-dependent kinase Cdk8, and the tail module, which is required for positive and negative regulation of transcription, correct preinitiation complex formation in basal and activated transcription, and Mediator recruitment. Currently, the molecular mechanisms governing Mediator function remain largely undefined. Here we demonstrate an autoregulatory mechanism used by Mediator to repress transcription through the activity of distinct components of different modules. We show that the function of the tail module component Med3, which is required for transcription activation, is suppressed by the kinase activity of the Cdk8 module. Med3 interacts with, and is phosphorylated by, Cdk8; site-specific phosphorylation triggers interaction with and degradation by the Grr1 ubiquitin ligase, thereby preventing transcription activation. This active repression mechanism involving Grr1-dependent ubiquitination of Med3 offers a rationale for the substoichiometric levels of the tail module that are found in purified Mediator and the corresponding increase in tail components seen in cdk8 mutants.
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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.