Evidence map›Paper›PMID 37155846›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2023

Epstein-Barr virus LMP1 protein promotes proliferation and inhibits differentiation of epithelial cells via activation of YAP and TAZ.

Deo R Singh, Scott E Nelson, Abigail S Pawelski, Alisha S Kansra, Stuart A Fogarty, Jillian A Bristol, Makoto Ohashi, Eric C Johannsen, Shannon C Kenney

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. 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
5.2field-weighted citation impact, top 4% 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, 25 citations in OpenAlex.

  1. The diverse functions of viral microproteins.bioRxiv : the preprint server for biology · 2026
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  14. HPV18 E7 inhibits LATS1 kinase and activates YAP1 by degrading PTPN14.bioRxiv : the preprint server for biology · 2024
    Article
  15. Article
  16. 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

9 authors at 1 institution in 1 country.

Deo R SinghDepartment of Oncology, University of Wisconsin School of Medicine and Public Health, WIMR II, Madison, WI 53705.ORCID 0000-0001-9027-1813
Scott E NelsonDepartment of Oncology, University of Wisconsin School of Medicine and Public Health, WIMR II, Madison, WI 53705.ORCID 0000-0003-0084-1355
Abigail S PawelskiDepartment of Oncology, University of Wisconsin School of Medicine and Public Health, WIMR II, Madison, WI 53705.
Alisha S KansraDepartment of Oncology, University of Wisconsin School of Medicine and Public Health, WIMR II, Madison, WI 53705.ORCID 0000-0003-4233-2401
Stuart A FogartyDepartment of Oncology, University of Wisconsin School of Medicine and Public Health, WIMR II, Madison, WI 53705.
Jillian A BristolDepartment of Oncology, University of Wisconsin School of Medicine and Public Health, WIMR II, Madison, WI 53705.ORCID 0000-0001-6109-8126
Makoto OhashiDepartment of Oncology, University of Wisconsin School of Medicine and Public Health, WIMR II, Madison, WI 53705.
Eric C JohannsenDepartment of Oncology, University of Wisconsin School of Medicine and Public Health, WIMR II, Madison, WI 53705.
Shannon C KenneyDepartment of Oncology, University of Wisconsin School of Medicine and Public Health, WIMR II, Madison, WI 53705.
University of Wisconsin–Madison · US

Funding

Visualizing EBV and HCMV DNA Dynamics During InfectionP01CA022443 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Paul F. Lambert · 1985 to 2026
$53.1M
Effects of EBV Type on Viral ReactivationR01AI147060 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI KENNEY, SHANNON CELESTE · 2019 to 2023
$2.6M
Role of EBV Lytic Infection in Viral TumorigenesisR01CA229673 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI KENNEY, SHANNON CELESTE · 2019 to 2023
$2.5M
EBV LMP1/LMP2A Proteins Promote Hodgkin-like Lymphomas in Humanized MiceR01CA232616 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI KENNEY, SHANNON CELESTE · 2018 to 2022
$1.9M
NCI NIH HHS P01 CA022443NCI NIH HHS R01 CA229673NCI NIH HHS R01 CA232616NIAID NIH HHS R01 AI147060
6 · The paper itself

Abstract

Latent Epstein-Barr virus (EBV) infection promotes undifferentiated nasopharyngeal carcinomas (NPCs) in humans, but the mechanism(s) for this effect has been difficult to study because EBV cannot transform normal epithelial cells in vitro and the EBV genome is often lost when NPC cells are grown in culture. Here we show that the latent EBV protein, LMP1 (Latent membrane protein 1), induces cellular proliferation and inhibits spontaneous differentiation of telomerase-immortalized normal oral keratinocytes (NOKs) in growth factor-deficient conditions by increasing the activity of the Hippo pathway effectors, YAP (Yes-associated protein) and TAZ (Transcriptional coactivator with PDZ-binding motif). We demonstrate that LMP1 enhances YAP and TAZ activity in NOKs both by decreasing Hippo pathway-mediated serine phosphorylation of YAP and TAZ and increasing Src kinase-mediated Y357 phosphorylation of YAP. Furthermore, knockdown of YAP and TAZ is sufficient to reduce proliferation and promote differentiation in EBV-infected NOKs. We find that YAP and TAZ are also required for LMP1-induced epithelial-to-mesenchymal transition. Importantly, we demonstrate that ibrutinib (an FDA-approved BTK inhibitor that blocks YAP and TAZ activity through an off-target effect) restores spontaneous differentiation and inhibits proliferation of EBV-infected NOKs at clinically relevant doses. These results suggest that LMP1-induced YAP and TAZ activity contributes to the development of NPC.

Indexed as

Epstein-Barr Virus InfectionsNasopharyngeal NeoplasmsCell DifferentiationCell ProliferationEpithelial CellsHerpesvirus 4, HumanHumansTranscriptional Coactivator with PDZ-Binding Motif ProteinsViral Matrix ProteinsYAP-Signaling ProteinsEBV-associated membrane antigen, Epstein-Barr virusTranscriptional Coactivator with PDZ-Binding Motif ProteinsViral Matrix ProteinsWWTR1 protein, humanYAP-Signaling ProteinsEBVLMP1NPCTAZYAP

Identifiers

PMID37155846
PMCPMC10193989
OpenAlexW4375955939

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.