Evidence map›Paper›PMID 29028833›Full record

ArticlePLoS pathogens2017

Merkel cell polyomavirus recruits MYCL to the EP400 complex to promote oncogenesis.

Jingwei Cheng, Donglim Esther Park, Christian Berrios, Elizabeth A White, Reety Arora, Rosa Yoon, Timothy Branigan, Tengfei Xiao, Thomas Westerling, Alexander Federation and 10 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

86 citing papers in PubMed, 126 citations in OpenAlex.

  1. Article
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  5. Review
  6. Diagnostic Utility and Clinicopathologic Associations of Histone H3 Lysine 27 Trimethylation (H3K27me3) Immunohistochemistry for Merkel Cell Carcinoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2026
    Article
  7. Pharmacologic reversion of Merkel cell carcinoma via CBP/p300 inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  8. Article
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  14. Review
  15. Beyond the Limit: MYC Mediates Tumor Immune Escape.Pharmaceuticals (Basel, Switzerland) · 2025
    Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

26 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

20 authors at 4 institutions in 1 country.

Jingwei ChengDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
Donglim Esther ParkDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
Christian BerriosDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
Elizabeth A WhiteDepartment of Microbiology and Immunobiology, Harvard Medical School; Boston, Massachusetts, United States of America.
Reety AroraDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.ORCID http://orcid.org/0000-0002-1871-9297
Rosa YoonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.ORCID http://orcid.org/0000-0002-5497-5925
Timothy BraniganDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.ORCID http://orcid.org/0000-0002-8641-5332
Tengfei XiaoDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
Thomas WesterlingDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
Alexander FederationDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.ORCID http://orcid.org/0000-0002-7771-1148
Rhamy ZeidDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
Benjamin StroberDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
Selene K SwansonStowers Institute for Medical Research, Kansas City, Missouri, United States of America.ORCID http://orcid.org/0000-0002-2461-2744
Laurence FlorensStowers Institute for Medical Research, Kansas City, Missouri, United States of America.ORCID http://orcid.org/0000-0002-9310-6650
James E BradnerDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
Myles BrownDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.ORCID http://orcid.org/0000-0002-8213-1658
Peter M HowleyDepartment of Microbiology and Immunobiology, Harvard Medical School; Boston, Massachusetts, United States of America.
Megha PadiDepartment of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
Michael P WashburnStowers Institute for Medical Research, Kansas City, Missouri, United States of America.
James A DeCaprioDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.ORCID http://orcid.org/0000-0002-0896-167X
Harvard University · USBrigham and Women's Hospital · USDana-Farber Cancer Institute · USStowers Institute for Medical Research · US

Funding

VIRAL ONCOPROTEIN PERTURBATION OF RB/E2F PATHWAYP01CA050661 · NCI · DANA-FARBER CANCER INSTITUTE · PI ROBERTS, THOMAS M · 1989 to 2013
$35.8M
PROJECT 4: Interrogating PP2A Signaling in Human CancersP01CA203655 · NCI · DANA-FARBER CANCER INST · PI DECAPRIO, JAMES A. · 2017 to 2021
$8.0M
Molecular Biology of Oncogenic PapillomavirusesR35CA197262 · NCI · HARVARD MEDICAL SCHOOL · PI HOWLEY, PETER M · 2016 to 2022
$7.1M
RB-RELATED PROTEINS IN SV4OT AND E1A TRANSFORMATIONR01CA063113 · NCI · DANA-FARBER CANCER INSTITUTE · PI DECAPRIO, JAMES A. · 1994 to 2018
$5.0M
Transforming Mechanisms of Merkel Cell Polyoma VirusR01CA173023 · NCI · DANA-FARBER CANCER INST · PI DECAPRIO, JAMES A. · 2013 to 2019
$2.3M
Modeling phenotypic transitions in gene expression state spaceK25HG006031 · NHGRI · DANA-FARBER CANCER INST · PI PADI, MEGHA · 2011 to 2015
$890k
Investigating the Mechanism of B-myb Dependent Gene ExpressionF31CA189328 · NCI · HARVARD MEDICAL SCHOOL · PI BRANIGAN, TIMOTHY BRUCE · 2014 to 2016
$101k
Investigating Merkel Cell Polyomavirus Small T Antigen-Host InteractionsF31CA177274 · NCI · HARVARD MEDICAL SCHOOL · PI BERRIOS, CHRISTIAN JOSE · 2013 to 2015
$100k
T antigens inhibit Notch to promote Merkel cell carcinoma in skin stem cellsF31CA213464 · NCI · HARVARD MEDICAL SCHOOL · PI PARK, DONGLIM ESTHER · 2017 to 2018
$64k
NCI NIH HHS F31 CA177274NCI NIH HHS F31 CA189328NCI NIH HHS F31 CA213464NCI NIH HHS P01 CA050661NCI NIH HHS P01 CA203655NCI NIH HHS R01 CA063113NCI NIH HHS R01 CA173023NCI NIH HHS R35 CA197262NHGRI NIH HHS K25 HG006031Wellcome Trust
6 · The paper itself

Abstract

Merkel cell carcinoma (MCC) frequently contains integrated copies of Merkel cell polyomavirus DNA that express a truncated form of Large T antigen (LT) and an intact Small T antigen (ST). While LT binds RB and inactivates its tumor suppressor function, it is less clear how ST contributes to MCC tumorigenesis. Here we show that ST binds specifically to the MYC homolog MYCL (L-MYC) and recruits it to the 15-component EP400 histone acetyltransferase and chromatin remodeling complex. We performed a large-scale immunoprecipitation for ST and identified co-precipitating proteins by mass spectrometry. In addition to protein phosphatase 2A (PP2A) subunits, we identified MYCL and its heterodimeric partner MAX plus the EP400 complex. Immunoprecipitation for MAX and EP400 complex components confirmed their association with ST. We determined that the ST-MYCL-EP400 complex binds together to specific gene promoters and activates their expression by integrating chromatin immunoprecipitation with sequencing (ChIP-seq) and RNA-seq. MYCL and EP400 were required for maintenance of cell viability and cooperated with ST to promote gene expression in MCC cell lines. A genome-wide CRISPR-Cas9 screen confirmed the requirement for MYCL and EP400 in MCPyV-positive MCC cell lines. We demonstrate that ST can activate gene expression in a EP400 and MYCL dependent manner and this activity contributes to cellular transformation and generation of induced pluripotent stem cells.

Indexed as

Antigens, Polyomavirus TransformingAntigens, Viral, TumorCarcinoma, Merkel CellCell Line, TumorCell Transformation, ViralDNA-Binding ProteinsDNA HelicasesGene Expression Regulation, NeoplasticHumansImmunoblottingImmunoprecipitationMerkel cell polyomavirusPolyomavirus InfectionsProto-Oncogene Proteins c-mycTumor Virus InfectionsAntigens, Polyomavirus TransformingAntigens, Viral, TumorDNA-Binding ProteinsDNA HelicasesEP400 protein, humanMYCL protein, humanProto-Oncogene Proteins c-myc

Identifiers

PMID29028833
PMCPMC5640240
OpenAlexW2762776228

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Read underepoch 390

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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.