Evidence map›Paper›PMID 26727473›Full record

ArticlePLoS pathogens2016

Papillomavirus-Associated Tumor Formation Critically Depends on c-Fos Expression Induced by Viral Protein E2 and Bromodomain Protein Brd4.

Maria Delcuratolo, Jasmin Fertey, Markus Schneider, Johanna Schuetz, Natalie Leiprecht, Benjamin Hudjetz, Stephan Brodbeck, Silke Corall, Marcel Dreer, Roxana Michaela Schwab and 5 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

16 citing papers in PubMed, 31 citations in OpenAlex.

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  16. The Interaction Between Human Papillomaviruses and the Stromal Microenvironment.Progress in molecular biology and translational science · 2016
    Review
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

15 authors at 2 institutions in 2 countries.

Maria DelcuratoloDivision of Experimental Virology, Institute of Medical Virology, University Hospital Tübingen, Tübingen, Germany.
Jasmin FerteyDivision of Experimental Virology, Institute of Medical Virology, University Hospital Tübingen, Tübingen, Germany.
Markus SchneiderDivision of Experimental Virology, Institute of Medical Virology, University Hospital Tübingen, Tübingen, Germany.
Johanna SchuetzDivision of Experimental Virology, Institute of Medical Virology, University Hospital Tübingen, Tübingen, Germany.
Natalie LeiprechtDivision of Experimental Virology, Institute of Medical Virology, University Hospital Tübingen, Tübingen, Germany.
Benjamin HudjetzDivision of Experimental Virology, Institute of Medical Virology, University Hospital Tübingen, Tübingen, Germany.
Stephan BrodbeckDivision of Experimental Virology, Institute of Medical Virology, University Hospital Tübingen, Tübingen, Germany.
Silke CorallDivision of Experimental Virology, Institute of Medical Virology, University Hospital Tübingen, Tübingen, Germany.
Marcel DreerDivision of Experimental Virology, Institute of Medical Virology, University Hospital Tübingen, Tübingen, Germany.
Roxana Michaela SchwabDivision of Experimental Virology, Institute of Medical Virology, University Hospital Tübingen, Tübingen, Germany.
Martin GrimmDepartment of Oral and Maxillofacial Surgery, University Hospital Tübingen, Tübingen, Germany.
Shwu-Yuan WuUniversity of Texas Southwestern Medical Center, Simmons Comprehensive Cancer Center, Department of Biochemistry, Department of Pharmacology, Dallas, Texas, United States of America.
Frank StubenrauchDivision of Experimental Virology, Institute of Medical Virology, University Hospital Tübingen, Tübingen, Germany.
Cheng-Ming ChiangUniversity of Texas Southwestern Medical Center, Simmons Comprehensive Cancer Center, Department of Biochemistry, Department of Pharmacology, Dallas, Texas, United States of America.
Thomas IftnerDivision of Experimental Virology, Institute of Medical Virology, University Hospital Tübingen, Tübingen, Germany.
The University of Texas Southwestern Medical Center · USUniversity Children's Hospital Tübingen · DE

Funding

E2-Cellular Complexes in HPV Chromatin TranscriptionR01CA103867 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI CHIANG, CHENG-MING · 2004 to 2017
$4.0M
NCI NIH HHS CA103867NCI NIH HHS R01 CA103867
6 · The paper itself

Abstract

We investigated the mechanism of how the papillomavirus E2 transcription factor can activate promoters through activator protein (AP)1 binding sites. Using an unbiased approach with an inducible cell line expressing the viral transcription factor E2 and transcriptome analysis, we found that E2 induces the expression of the two AP1 components c-Fos and FosB in a Brd4-dependent manner. In vitro RNA interference confirmed that c-Fos is one of the AP1 members driving the expression of viral oncogenes E6/E7. Mutation analysis and in vivo RNA interference identified an essential role for c-Fos/AP1 and also for the bromodomain protein Brd4 for papillomavirus-induced tumorigenesis. Lastly, chromatin immunoprecipitation analysis demonstrated that E2 binds together with Brd4 to a canonical E2 binding site (E2BS) in the promoter of c-Fos, thus activating c-Fos expression. Thus, we identified a novel way how E2 activates the viral oncogene promoter and show that E2 may act as a viral oncogene by direct activation of c-Fos involved in skin tumorigenesis.

Indexed as

AnimalsCell LineCell Transformation, ViralChromatin ImmunoprecipitationDisease Models, AnimalDNA-Binding ProteinsDNA Mutational AnalysisElectrophoretic Mobility Shift AssayGene Expression Regulation, ViralGenes, ViralImmunoprecipitationNuclear ProteinsOncogene Proteins, ViralOncogenesPapillomaviridaePapillomavirus InfectionsDNA-Binding ProteinsNuclear Proteinsoncogene protein E2, Human papillomavirus type 1Oncogene Proteins, ViralProto-Oncogene Proteins c-fosTranscription Factors

Identifiers

PMID26727473
PMCPMC4699637
OpenAlexW2231279381

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.