Evidence map›Paper›PMID 18337573›Full record

ArticleJournal of virology2008

Dimerization of the human papillomavirus type 16 E2 N terminus results in DNA looping within the upstream regulatory region.

Elena E Hernandez-Ramon, Julie E Burns, Wenke Zhang, Hannah F Walker, Stephanie Allen, Alfred A Antson, Norman J Maitland

Abstract read
In one paragraph

Article in Journal of virology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

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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

7 authors.

Elena E Hernandez-RamonYCR Cancer Research Unit, Department of Biology (Area 13), University of York, Heslington, York, YO10 5DD United Kingdom.
Julie E Burns
Wenke Zhang
Hannah F Walker
Stephanie Allen
Alfred A Antson
Norman J Maitland

Funding

Wellcome Trust 077371Wellcome Trust 081916
6 · The paper itself

Abstract

Papillomavirus E2 proteins play a central role in regulating viral gene expression and replication. DNA-binding activity is associated with the C-terminal domain of E2, which forms a stable dimer, while the N-terminal domain is responsible for E2's replication and transactivation functions. The crystal structure of the latter domain revealed a second dimerization interface on E2 which may be responsible for DNA loop formation in the regulatory region of the human papillomavirus (HPV) genome. We investigated the biological significance of the N-terminal dimerization by introducing single amino acid substitutions into the dimerization interface. As expected, these substitutions did not influence the C-terminal dimerization and DNA-binding functions of E2. However, the mutations led to reduced transactivation of a synthetic E2-responsive reporter gene, while HPV DNA replication was unaffected. The effect of the mutations on DNA looping was visualized by atomic force microscopy. While wild-type E2 was able to generate DNA loops, all three mutant E2 proteins were defective in this ability. Our results suggest that N-terminal dimerization plays a role in E2-mediated transactivation, probably via DNA looping, a common mechanism for remote regulation of gene transcription.

Indexed as

Amino Acid SubstitutionArtificial Gene FusionCell LineDimerizationDNA-Binding ProteinsDNA, ViralElectrophoretic Mobility Shift AssayGenes, ReporterGreen Fluorescent ProteinsHuman papillomavirus 16HumansMicroscopy, Atomic ForceModels, BiologicalModels, MolecularMutagenesis, Site-DirectedOncogene Proteins, ViralDNA-Binding ProteinsDNA, ViralE2 protein, Human papillomavirus type 16enhanced green fluorescent proteinGreen Fluorescent ProteinsOncogene Proteins, Viral

Identifiers

PMID18337573
PMCPMC2346762

What OpenQuestion holds

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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.