ArticleScience advances2021
Structure and noncanonical Cdk8 activation mechanism within an Argonaute-containing Mediator kinase module.
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Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40citing papers in PubMed
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Who cites it
40 citing papers in PubMed, 58 citations in OpenAlex.
- Cyclins and Cyclin-Dependent Kinases: Structure, Biological Functions, and Innovative Targeting Strategies in Cancer.MedComm · 2026Review
- Vitamin D3 ameliorates R-loop-induced replication stress and chromosomal instability in MED12-mutant uterine fibroids.Scientific reports · 2026Article
- Cryo-EM structures of the CDK11-cyclin L-SAP30BP complex reveal mechanisms of CDK11 regulation.Nature communications · 2026Article
- Vitamin D3 ameliorates R-loop-induced replication stress and chromosomal instability in MED12-mutant uterine fibroids.Research square · 2026Article
- Nutrition and Uterine Fibroids: Clinical Impact and Emerging Therapeutic Perspectives.Journal of clinical medicine · 2025Review
- UTERINE FIBROIDS.Physiological reviews · 2025Review
- Structural and evolutionary determinants of Argonaute function.Nucleic acids research · 2025Article
- The Mediator Complex: A Regulatory Hub for Transcriptional Activity of Nuclear Receptors.Cells · 2025Review
- The Mediator Kinase Module regulates cell cycle re-entry and transcriptional responses following DNA damage.bioRxiv : the preprint server for biology · 2025Article
- Review
- Mediator kinase inhibition drives myometrial stem cell differentiation and the uterine fibroid phenotype through super-enhancer reprogramming.Journal of molecular medicine (Berlin, Germany) · 2025Article
- The CDK8 kinase module: A novel player in the transcription of translation initiation and ribosomal genes.Molecular biology of the cell · 2025Article
- Mediator kinase inhibition drives myometrial stem cell differentiation and the uterine fibroid phenotype through super-enhancer reprogramming.Research square · 2024Article
- Distinct effects of CDK8 module subunits on cellular growth and proliferation in Drosophila.Development (Cambridge, England) · 2024Article
- Med13 is required for efficient P-body recruitment and autophagic degradation of Edc3 following nitrogen starvation.Molecular biology of the cell · 2024Article
- Structural basis of the human transcriptional Mediator regulated by its dissociable kinase module.Molecular cell · 2024Article
- Structures and compositional dynamics of Mediator in transcription regulation.Current opinion in structural biology · 2024Review
- An IDR-dependent mechanism for nuclear receptor control of Mediator interaction with RNA polymerase II.Molecular cell · 2024Article
- A novel and ubiquitous miRNA-involved regulatory module ensures precise phosphorylation of RNA polymerase II and proper transcription.PLoS pathogens · 2024Article
- Ksp1 is an autophagic receptor protein for the Snx4-assisted autophagy of Ssn2/Med13.Autophagy · 2024Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 1 country.
Yi-Chuan LiDepartment of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID 0000-0002-1795-1051
Ti-Chun ChaoDepartment of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID 0000-0001-6154-929X
Hee Jong KimBiochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-0823-5301
Timothy CholkoDepartment of Chemistry, University of California, Riverside, CA, USA.ORCID 0000-0003-4431-8128
Shin-Fu ChenDepartment of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID 0000-0003-2551-0755
Guojie LiDepartment of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID 0000-0002-0524-961X
Laura SnyderDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Kotaro NakanishiDepartment of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA.ORCID 0000-0002-9857-6010
Chia-En ChangDepartment of Chemistry, University of California, Riverside, CA, USA.ORCID 0000-0002-6504-8529
Kenji MurakamiDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-2017-5575
Benjamin A GarciaDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Thomas G BoyerDepartment of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. kuang-lei.tsai@uth.tmc.edu boyer@uthscsa.edu.ORCID 0000-0002-9164-8712
Kuang-Lei TsaiDepartment of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA. kuang-lei.tsai@uth.tmc.edu boyer@uthscsa.edu.ORCID 0000-0002-5428-4219
The University of Texas Health Science Center at Houston · USUniversity of Pennsylvania · USUniversity of California, Riverside · USThe Ohio State University · USThe University of Texas Health Science Center at San Antonio · USThe University of Texas MD Anderson Cancer Center · US
Funding
STRUCTURAL BASIS FOR EPIGENETICS IN AGING AND LONGEVITYP01AG031862 · NIA · WISTAR INSTITUTE · PI GARCIA, BENJAMIN A · 2008 to 2022
$28.3MShared Resources Core 2: Quantitative Proteomics CoreP01CA196539 · NCI · ROCKEFELLER UNIVERSITY · PI MUIR, TOM · 2015 to 2024
$17.6MViral modulation of epitranscriptomic mechanismsR01AI118891 · NIAID · WASHINGTON UNIVERSITY · PI GARCIA, BENJAMIN A, WEITZMAN, MATTHEW D. · 2015 to 2025
$5.4MHypovitaminosis D promotes MED12-associated genomic instability in uterine fibroidsR01HD094378 · NICHD · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI AL-HENDY, AYMAN, BOYER, THOMAS G · 2018 to 2022
$4.2MFunctional and structural studies of the transition from transcription initiation to elongationR01GM123233 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI MURAKAMI, KENJI · 2017 to 2025
$3.6MMolecular basis of MED12 in the pathogenesis of uterine fibroidsR01HD087417 · NICHD · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI THOMAS G BOYER · 2017 to 2026
$3.4MTarget specificity of human RNA-induced silencing complexR01GM124320 · NIGMS · OHIO STATE UNIVERSITY · PI NAKANISHI, KOTARO · 2017 to 2025
$3.1MNext-Generation GPU Computing Resource for Simulating Ligand-Protein Binding Kinetics/MechanismR01GM109045 · NIGMS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI CHANG, CHIA-EN · 2014 to 2023
$2.8MPredoctoral Training at the Chemistry-Biology InterfaceT32GM133398 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI Ronen Marmorstein, Ernest James Petersson · 2020 to 2026
$2.4MStructural insights into the Argonaute-containing CDK8 complexR01GM143587 · NIGMS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI TSAI, KUANG-LEI · 2021 to 2025
$1.7MUnderstanding the Role of Combinatorial Histone PTM PatternsR01GM110174 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI GARCIA, BENJAMIN A · 2014 to 2017
$1.3MComputational Resource for Structural Biology and Molecular BiophysicsS10OD023592 · OD · UNIVERSITY OF PENNSYLVANIA · PI SHARP, KIM A · 2017 to 2017
$402kNCI NIH HHS P01 CA196539NIAID NIH HHS R01 AI118891NIA NIH HHS P01 AG031862NICHD NIH HHS R01 HD087417NICHD NIH HHS R01 HD094378NIGMS NIH HHS R01 GM109045NIGMS NIH HHS R01 GM110174NIGMS NIH HHS R01 GM123233NIGMS NIH HHS R01 GM124320NIGMS NIH HHS R01 GM143587NIGMS NIH HHS T32 GM133398NIH HHS S10 OD023592
Abstract
The Cdk8 kinase module (CKM) in Mediator, comprising Med13, Med12, CycC, and Cdk8, regulates RNA polymerase II transcription through kinase-dependent and -independent functions. Numerous pathogenic mutations causative for neurodevelopmental disorders and cancer congregate in CKM subunits. However, the structure of the intact CKM and the mechanism by which Cdk8 is non-canonically activated and functionally affected by oncogenic CKM alterations are poorly understood. Here, we report a cryo-electron microscopy structure of
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