Evidence map›Paper›PMID 27007123›Full record

ArticleJournal of neurovirology2016

The Brd4 acetyllysine-binding protein is involved in activation of polyomavirus JC.

Hassen S Wollebo, Anna Bellizzi, Dominique H Cossari, Julian Salkind, Mahmut Safak, Martyn K White

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neurovirology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.4field-weighted citation impact, top 17% 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

10 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Human polyomaviruses and cancer: an overview.Clinics (Sao Paulo, Brazil) · 2018
    Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
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

6 authors at 1 institution in 1 country.

Hassen S WolleboCenter for Neurovirology, Department of Neuroscience, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA, 19140, USA.
Anna BellizziCenter for Neurovirology, Department of Neuroscience, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA, 19140, USA.
Dominique H CossariCenter for Neurovirology, Department of Neuroscience, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA, 19140, USA.
Julian SalkindCenter for Neurovirology, Department of Neuroscience, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA, 19140, USA.
Mahmut SafakCenter for Neurovirology, Department of Neuroscience, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA, 19140, USA.
Martyn K WhiteCenter for Neurovirology, Department of Neuroscience, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA, 19140, USA. martyn.white@temple.edu.
Temple University · US

Funding

Viral Gene Editing and Bioinformatics Core for Institution # 269291P30MH092177 · NIMH · TEMPLE UNIV OF THE COMMONWEALTH · PI Ilker Kudret Sariyer · 2011 to 2026
$24.9M
Temple University Minority Access to Research Careers (MARC) programT34GM087239 · NIGMS · TEMPLE UNIV OF THE COMMONWEALTH · PI TANAKA, JACQUELINE C · 2009 to 2018
$5.2M
Cytokine regulation of JC virus latency and reactivationR01AI077460 · NIAID · TEMPLE UNIV OF THE COMMONWEALTH · PI WHITE, MARTYN K · 2008 to 2016
$3.2M
NIAID NIH HHS R01 AI077460NIGMS NIH HHS T34 GM087239NIMH NIH HHS P30 MH092177
6 · The paper itself

Abstract

Brd4 is an epigenetic reader protein and a member of the BET (bromodomain and extra terminal domain) family of proteins with two bromodomains that recognize acetylated lysine residues. Brd4 specifically binds to acetylated transcription factor NF-κB p65 and coactivates transcription. Polyomavirus JC (JCV) is regulated by a noncoding control region (NCCR) containing promoter/enhancer elements for viral gene expression including a binding site for NF-κB, which responds to proinflammatory cytokines such as TNF-α, the DNA damage response, calcium signaling and acetylation of the NF-κB p65 subunit on lysine residues K218 and K221. Earlier studies indicated that NF-κB is involved in the reactivation of persistent/latent JCV in glial cells to cause progressive multifocal leukoencephalopathy (PML), a severe demyelinating disease of the brain caused by replication of JCV in glial cells. To investigate the mechanism of action of NF-κB acetylation on JCV transcription, we examined Brd4 and found that JCV early transcription was stimulated by Brd4 via the JCV NF-κB site and that p65 K218 and K221 were involved. Treatment with the Brd4 inhibitor JQ1(+) or mutation of either K218 or K221 to glutamine (K218R or K221) inhibited this stimulation and decreased the proportion of p65 in the nucleus. We conclude that Brd4 is involved in the regulation of the activation status of JCV in glial cells.

Indexed as

Host-Pathogen InteractionsAcetylationAzepinesBromodomain Containing ProteinsCell Cycle ProteinsCell Line, TumorCell NucleusEpigenesis, GeneticGenes, ReporterHumansJC VirusLuciferasesMutationNeurogliaNuclear ProteinsProtein BindingAzepinesBRD4 protein, humanBromodomain Containing ProteinsCell Cycle Proteins(+)-JQ1 compoundLuciferasesNuclear ProteinsTranscription Factor RelATranscription FactorsTriazolesTumor Necrosis Factor-alphaEpigenetic regulationJC virusProgressive multifocal leukoencephalopathyProtein acetylationViral persistenceViral reactivation

Identifiers

PMID27007123
PMCPMC5035168
OpenAlexW2309343960

What OpenQuestion holds

Textmetadata
LicenceTDM
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.