Evidence map›Paper›PMID 21543491›Full record

ArticleJournal of virology2011

Canonical NF-kappaB activation is essential for Epstein-Barr virus latent membrane protein 1 TES2/CTAR2 gene regulation.

Benjamin E Gewurz, Jessica C Mar, Megha Padi, Bo Zhao, Nicholas P Shinners, Kaoru Takasaki, Edward Bedoya, James Y Zou, Ellen Cahir-McFarland, John Quackenbush and 1 more

Abstract read
In one paragraph

Article in Journal of virology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
1.0field-weighted citation impact, top 23% 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

36 citing papers in PubMed, 50 citations in OpenAlex.

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  13. Structure and Emerging Functions of LRCH Proteins in Leukocyte Biology.Frontiers in cell and developmental biology · 2020
    Review
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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

11 authors at 3 institutions in 1 country.

Benjamin E GewurzChanning Laboratory, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA.
Jessica C Mar
Megha Padi
Bo Zhao
Nicholas P Shinners
Kaoru Takasaki
Edward Bedoya
James Y Zou
Ellen Cahir-McFarland
John Quackenbush
Elliott Kieff
Harvard University · USDana-Farber Cancer Institute · USBrigham and Women's Hospital · US

Funding

Genomic Analysis of Network Perturbations in Human DiseaseP50HG004233 · NHGRI · DANA-FARBER CANCER INST · PI VIDAL, MARC · 2007 to 2017
$31.6M
Epstein-Barr Virus LMP-1 Mediated OncongenicityR01CA085180 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI KIEFF, ELLIOTT D · 2000 to 2016
$10.6M
VIRUS-HOST INTERACTIONS IN CANCERT32CA009031 · NCI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI KIEFF, ELLIOTT D · 1985 to 2009
$2.4M
Genetic and Proteomic Analysis of Epstein-Barr Virus LMP1 Activation of NF-kBK08CA140780 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI GEWURZ, BENJAMIN ELISON · 2010 to 2014
$900k
NCI NIH HHS 1K08CA140780-01NCI NIH HHS 5R01CA085180-10NCI NIH HHS 5T32CA009031-33NCI NIH HHS K08 CA140780NCI NIH HHS R01 CA085180NCI NIH HHS T32 CA009031NHGRI NIH HHS 5P50HG004233-04NHGRI NIH HHS P50 HG004233
6 · The paper itself

Abstract

Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) transforms rodent fibroblasts and is expressed in most EBV-associated malignancies. LMP1 (transformation effector site 2 [TES2]/C-terminal activation region 2 [CTAR2]) activates NF-κB, p38, Jun N-terminal protein kinase (JNK), extracellular signal-regulated kinase (ERK), and interferon regulatory factor 7 (IRF7) pathways. We have investigated LMP1 TES2 genome-wide RNA effects at 4 time points after LMP1 TES2 expression in HEK-293 cells. By using a false discovery rate (FDR) of <0.001 after correction for multiple hypotheses, LMP1 TES2 caused >2-fold changes in 1,916 mRNAs; 1,479 RNAs were upregulated and 437 were downregulated. In contrast to tumor necrosis factor alpha (TNF-α) stimulation, which transiently upregulates many target genes, LMP1 TES2 maintained most RNA effects through the time course, despite robust and sustained induction of negative feedback regulators, such as IκBα and A20. LMP1 TES2-regulated RNAs encode many NF-κB signaling proteins and secondary interacting proteins. Consequently, many LMP1 TES2-regulated RNAs encode proteins that form an extensive interactome. Gene set enrichment analyses found LMP1 TES2-upregulated genes to be significantly enriched for pathways in cancer, B- and T-cell receptor signaling, and Toll-like receptor signaling. Surprisingly, LMP1 TES2 and IκBα superrepressor coexpression decreased LMP1 TES2 RNA effects to only 5 RNAs, with FDRs of <0.001-fold and >2-fold changes. Thus, canonical NF-κB activation is critical for almost all LMP1 TES2 RNA effects in HEK-293 cells and a more significant therapeutic target than previously appreciated.

Indexed as

Gene Expression RegulationHEK293 CellsHerpesvirus 4, HumanHumansNF-kappa BProteinsRNASignal TransductionUp-RegulationViral Matrix ProteinsEBV-associated membrane antigen, Epstein-Barr virusNF-kappa BProteinsRNAViral Matrix Proteins

Identifiers

PMID21543491
PMCPMC3126495
OpenAlexW2133950973

What OpenQuestion 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 OpenQuestion graph.