Evidence map›Paper›PMID 41402279›Full record

ArticleNature communications2025

Transcriptional regulation of protein synthesis by mediator kinase represents a therapeutic vulnerability in MYC-driven medulloblastoma.

Dong Wang, Caitlin Ritz, Yuhuan Luo, Ammu Suresh, Angela Pierce, Bethany Veo, Breauna Brunt, Nathan Dahl, Natalie Serkova, Sujatha Venkataraman and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Dong WangDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Caitlin RitzDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Yuhuan LuoDepartment of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Ammu SureshDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Angela PierceDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.ORCID http://orcid.org/0000-0003-0848-0494
Bethany VeoDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Breauna BruntDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Nathan DahlDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.ORCID http://orcid.org/0000-0003-2555-1741
Natalie SerkovaDepartment of Radiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.ORCID http://orcid.org/0000-0002-4573-3895
Sujatha VenkataramanDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Etienne DanisBiostatistics and Bioinformatics Shared Resource, University of Colorado Cancer Center, Aurora, CO, USA.
Kamil KusRYVU Therapeutics, Krakow, Poland.
Milena MazanRYVU Therapeutics, Krakow, Poland.ORCID http://orcid.org/0009-0005-9956-909X
Tomasz RzymskiRYVU Therapeutics, Krakow, Poland.
Rajeev VibhakarDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. rajeev.vibhakar@cuanschutz.edu.ORCID http://orcid.org/0000-0002-5949-3896

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
NCI NIH HHS P30 CA046934
6 · The paper itself

Abstract

MYC-driven medulloblastoma (MB) is a highly aggressive brain tumor with poor prognosis and limited treatment options. Through CRISPR-Cas9 screening, we identify the Mediator-associated kinase CDK8 as a critical regulator of MYC-driven MB. Both genetic loss and pharmacological inhibition of CDK8 impair MB tumor growth. Moreover, we find that CDK8 cooperates with MYC to sustain the MYC-mediated translational program, as CDK8 depletion induces pronounced transcriptional changes in translation-associated gene sets, reduces ribosome biogenesis, and impairs protein synthesis. Mechanistically, CDK8 regulates the occupancy of RNA polymerase II at specific chromatin loci, facilitating epigenetic alterations that promote the transcription of ribosomal genes. Furthermore, combined inhibition of CDK8 and mTOR synergistically enhances therapeutic efficacy in vivo, leading to more pronounced tumor growth suppression. Overall, our findings establish a functional link between CDK8-mediated transcriptional regulation and mRNA translation, suggesting a promising therapeutic approach targeting protein synthesis for MYC-driven MB.

Indexed as

Cerebellar NeoplasmsCyclin-Dependent Kinase 8Gene Expression Regulation, NeoplasticMedulloblastomaProtein BiosynthesisProto-Oncogene Proteins c-mycAnimalsCell Line, TumorCRISPR-Cas SystemsHumansMiceRNA Polymerase IITOR Serine-Threonine KinasesTranscription, GeneticXenograft Model Antitumor AssaysCDK8 protein, humanCyclin-Dependent Kinase 8MTOR protein, humanMYC protein, humanProto-Oncogene Proteins c-mycRNA Polymerase IITOR Serine-Threonine Kinases

Identifiers

PMID41402279
PMCPMC12708665

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.