Evidence map›Paper›PMID 30842331›Full record

ArticleJournal of virology2019

Phosphorylation of a Conserved Tyrosine in the Papillomavirus E2 Protein Regulates Brd4 Binding and Viral Replication.

Marsha DeSmet, Leny Jose, Nasro Isaq, Elliot J Androphy

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
0.9field-weighted citation impact, top 26% 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

17 citing papers in PubMed, 20 citations in OpenAlex.

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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

4 authors at 1 institution in 1 country.

Marsha DeSmet *Department of Dermatology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Leny Jose *Department of Dermatology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Nasro IsaqDepartment of Dermatology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Elliot J AndrophyDepartment of Dermatology, Indiana University School of Medicine, Indianapolis, Indiana, USA eandro@iu.edu.ORCID 0000-0002-8104-0703
Indiana University School of Medicine

Funding

Immunology and Infectious Diseases Training ProgramT32AI060519 · NIAID · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI MARK H KAPLAN · 2004 to 2026
$6.0M
CONTROL OF PAPILLOMAVIRUS EXPRESSION AND TRANSFORMATIONR01CA058376 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ANDROPHY, ELLIOT J. · 1993 to 2019
$5.7M
NCI NIH HHS R01 CA058376NIAID NIH HHS T32 AI060519
6 · The paper itself

Abstract

The papillomavirus (PV) E2 protein coordinates viral transcription and genome replication. Following a strategy to identify amino acids in E2 that are posttranslationally modified, we reported that tyrosine kinase fibroblast growth factor receptor 3 (FGFR3) complexes with and phosphorylates E2, which inhibits viral DNA replication. Here, we present several lines of evidence indicating that tyrosine (Y) 138 of HPV-31 E2 is a substrate of FGFR3. The active form of FGFR3 bound to and phosphorylated the region of amino acids (aa) 107 to 175 in HPV-31 E2. The E2 phenylalanine (F) mutant Y138F displayed reduced FGFR3-induced phosphotyrosine. A constitutive kinase-active FGFR3 inhibited wild-type (WT) E2-induced E1-dependent DNA replication, while the 138F mutant retained activity. The tyrosine to glutamic acid (E) mutant Y138E, which can mimic phosphotyrosine, failed to induce transient DNA replication, although it maintained the ability to bind and localize the viral DNA helicase E1 to the viral origin. The bromodomain-containing protein 4 (Brd4) binds to E2 and is necessary for initiation of viral DNA synthesis. Interestingly, the Y138E protein coimmunoprecipitated with full-length Brd4 but was defective for association with its C-terminal domain (CTD). These results imply that the activity of the FGFR3 kinase in the infected epithelial cell restricts the HPV replication program through phosphorylation of E2 at Y138, which interferes with E2 binding to the Brd4 CTD, and that this interaction is required for initiation of viral DNA synthesis.

Indexed as

Bromodomain Containing ProteinsCell Cycle ProteinsDNA-Binding ProteinsDNA HelicasesDNA ReplicationDNA, ViralHEK293 CellsHeLa CellsHumansNuclear ProteinsOncogene Proteins, ViralPapillomaviridaePapillomavirus InfectionsPhosphorylationProtein BindingReceptor, Fibroblast Growth Factor, Type 3BRD4 protein, humanBromodomain Containing ProteinsCell Cycle ProteinsDNA-Binding ProteinsDNA HelicasesDNA, ViralFGFR3 protein, humanNuclear Proteinsoncogene protein E2, Human papillomavirus type 1Oncogene Proteins, ViralReceptor, Fibroblast Growth Factor, Type 3Transcription FactorsTyrosineBrd4HPVkinasetyrosine phosphorylationviral replication

Identifiers

PMID30842331
PMCPMC6498050
OpenAlexW2921216986

What Socratic holds

Textmetadata
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 Socratic graph.