Evidence map›Paper›PMID 27050516›Full record

ArticleCell reports2016

Identification of Mediator Kinase Substrates in Human Cells using Cortistatin A and Quantitative Phosphoproteomics.

Zachary C Poss, Christopher C Ebmeier, Aaron T Odell, Anupong Tangpeerachaikul, Thomas Lee, Henry E Pelish, Matthew D Shair, Robin D Dowell, William M Old, Dylan J Taatjes

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed
8.5field-weighted citation impact, top 2% of its field
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

99 citing papers in PubMed, 163 citations in OpenAlex.

  1. Article
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  8. UTERINE FIBROIDS.Physiological reviews · 2025
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  9. Dual Modes of Gene Regulation by CDK12.bioRxiv : the preprint server for biology · 2025
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  20. Review

39 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Zachary C PossDepartment of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80303, USA.
Christopher C EbmeierDepartment of Molecular, Cell, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Aaron T OdellDepartment of Molecular, Cell, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA; BioFrontiers Institute, University of Colorado, Boulder, CO 80309, USA.
Anupong TangpeerachaikulDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Thomas LeeDepartment of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80303, USA.
Henry E PelishDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Matthew D ShairDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Robin D DowellDepartment of Molecular, Cell, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA; BioFrontiers Institute, University of Colorado, Boulder, CO 80309, USA.
William M OldDepartment of Molecular, Cell, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Dylan J TaatjesDepartment of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80303, USA. Electronic address: taatjes@colorado.edu.
University of Colorado Boulder · USHarvard University · US

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
TRAINING IN SIGNAL TRANSDUCTION &CELL CYCLE REGULATIONT32GM008759 · NIGMS · UNIVERSITY OF COLORADO AT BOULDER · PI AHN, NATALIE G. · 2000 to 2020
$5.9M
Predoctoral Training Program in Signaling and Cellular Regulation INCLUDE Down Syndrome SupplementT32GM142607 · NIGMS · UNIVERSITY OF COLORADO · PI Sabrina Leigh Spencer, Tin Tin Su · 2021 to 2026
$3.6M
Directing the Mediator Complex: Bivalent approaches to Reconstituting or InhibitiR01CA170741 · NCI · YALE UNIVERSITY · PI SCHEPARTZ, ALANNA, TAATJES, DYLAN J · 2012 to 2016
$1.9M
Comprehensive Identification of CDK8 Kinase Targets Using SILAC PhosphoproteomicsR21CA175448 · NCI · UNIVERSITY OF COLORADO · PI OLD, WILLIAM MARLAND · 2014 to 2015
$355k
Characterization and regulation of the MED17-p53 binding interface.F31CA180419 · NCI · UNIVERSITY OF COLORADO · PI POSS, ZACHARY C. · 2013 to 2014
$62k
NCI NIH HHS F31 CA180419NCI NIH HHS P30 CA046934NCI NIH HHS P30-CA046934NCI NIH HHS R01 CA170741NCI NIH HHS R21 CA175448NIGMS NIH HHS T32 GM008759NIGMS NIH HHS T32 GM08759NIGMS NIH HHS T32 GM142607
6 · The paper itself

Abstract

Cortistatin A (CA) is a highly selective inhibitor of the Mediator kinases CDK8 and CDK19. Using CA, we now report a large-scale identification of Mediator kinase substrates in human cells (HCT116). We identified over 16,000 quantified phosphosites including 78 high-confidence Mediator kinase targets within 64 proteins, including DNA-binding transcription factors and proteins associated with chromatin, DNA repair, and RNA polymerase II. Although RNA-seq data correlated with Mediator kinase targets, the effects of CA on gene expression were limited and distinct from CDK8 or CDK19 knockdown. Quantitative proteome analyses, tracking around 7,000 proteins across six time points (0-24 hr), revealed that CA selectively affected pathways implicated in inflammation, growth, and metabolic regulation. Contrary to expectations, increased turnover of Mediator kinase targets was not generally observed. Collectively, these data support Mediator kinases as regulators of chromatin and RNA polymerase II activity and suggest their roles extend beyond transcription to metabolism and DNA repair.

Indexed as

Cyclin-Dependent KinasesGene Expression Regulation, NeoplasticGene Knockdown TechniquesHCT116 CellsHumansPhosphoproteinsPolycyclic CompoundsProtein Kinase InhibitorsProtein KinasesProteomeProteomicsReproducibility of ResultsSubstrate SpecificityTranscription, Geneticcortistatin ACyclin-Dependent KinasesPhosphoproteinsPolycyclic CompoundsProtein Kinase InhibitorsProtein KinasesProteomeCDK8-MediatorcholesterolMED13MED13LMediatorSILACSIRT1

Identifiers

PMID27050516
PMCPMC4833653
OpenAlexW2314789443

What OpenQuestion holds

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Registered trials

None linked

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.