Evidence map›Paper›PMID 25855980›Full record

ArticlePLoS pathogens2015

The EBNA3 family of Epstein-Barr virus nuclear proteins associates with the USP46/USP12 deubiquitination complexes to regulate lymphoblastoid cell line growth.

Makoto Ohashi, Amy M Holthaus, Michael A Calderwood, Chiou-Yan Lai, Bryan Krastins, David Sarracino, Eric Johannsen

Abstract read
In one paragraph

Article in PLoS pathogens, 2015. 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
–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

36 citing papers in PubMed.

  1. TRIM21 is a molecular rheostat for influenza A virus replication.bioRxiv : the preprint server for biology · 2026
    Article
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  4. Review
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  6. Review
  7. Applying Reverse Genetics to Study Measles Virus Interactions with the Host.Methods in molecular biology (Clifton, N.J.) · 2024
    Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

7 authors.

Makoto OhashiDepartments of Medicine and Oncology (McArdle Laboratory for Cancer Research), University of Wisconsin, Madison, Wisconsin, United States of America.
Amy M HolthausInfectious Disease Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
Michael A CalderwoodInfectious Disease Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
Chiou-Yan LaiInfectious Disease Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
Bryan KrastinsBiomarker Research Initiatives in Mass Spectrometry (BRIMS), Thermo Fisher Scientific, Cambridge, Massachusetts, United States of America.
David SarracinoBiomarker Research Initiatives in Mass Spectrometry (BRIMS), Thermo Fisher Scientific, Cambridge, Massachusetts, United States of America.
Eric JohannsenDepartments of Medicine and Oncology (McArdle Laboratory for Cancer Research), University of Wisconsin, Madison, Wisconsin, United States of America.

Funding

Epstein-Barr Virus Nuclear Proteins in B Cell Growth TransformationR01CA047006 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ZHAO, BO · 2002 to 2021
$12.1M
Epigenetic determinants of Epstein-Barr virus and cellular DNA in oral diseasesR01DE023939 · NIDCR · UNIVERSITY OF WISCONSIN-MADISON · PI JOHANNSEN, ERIC C, KENNEY, SHANNON CELESTE · 2013 to 2017
$2.9M
MOLECULAR BIOLOGY OF EPSTEIN-BARR VIRUS INFECTIONR35CA047006 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI KIEFF, ELLIOTT D · 1987 to 2000
$1.6M
NCI NIH HHS CA47006NCI NIH HHS R01 CA047006NCI NIH HHS R35 CA047006NIDCR NIH HHS R01 DE023939
6 · The paper itself

Abstract

The Epstein-Barr virus (EBV) nuclear proteins EBNA3A, EBNA3B, and EBNA3C interact with the cell DNA binding protein RBPJ and regulate cell and viral genes. Repression of the CDKN2A tumor suppressor gene products p16(INK4A) and p14(ARF) by EBNA3A and EBNA3C is critical for EBV mediated transformation of resting B lymphocytes into immortalized lymphoblastoid cell lines (LCLs). To define the composition of endogenous EBNA3 protein complexes, we generated lymphoblastoid cell lines (LCLs) expressing flag-HA tagged EBNA3A, EBNA3B, or EBNA3C and used tandem affinity purification to isolate each EBNA3 complex. Our results demonstrated that each EBNA3 protein forms a distinct complex with RBPJ. Mass-spectrometry revealed that the EBNA3A and EBNA3B complexes also contained the deubquitylation complex consisting of WDR48, WDR20, and USP46 (or its paralog USP12) and that EBNA3C complexes contained WDR48. Immunoprecipitation confirmed that EBNA3A, EBNA3B, and EBNA3C association with the USP46 complex. Using chromatin immunoprecipitation, we demonstrate that WDR48 and USP46 are recruited to the p14(ARF) promoter in an EBNA3C dependent manner. Mapping studies were consistent with WDR48 being the primary mediator of EBNA3 association with the DUB complex. By ChIP assay, WDR48 was recruited to the p14(ARF) promoter in an EBNA3C dependent manner. Importantly, WDR48 associated with EBNA3A and EBNA3C domains that are critical for LCL growth, suggesting a role for USP46/USP12 in EBV induced growth transformation.

Indexed as

Blotting, WesternCell LineCell ProliferationCell Transformation, ViralChromatin ImmunoprecipitationEndopeptidasesEpstein-Barr Virus Nuclear AntigensGene Expression Regulation, ViralHerpesvirus 4, HumanHumansImmunoprecipitationMass SpectrometryUbiquitin ThiolesteraseEBNA-3A antigenEBNA-3B antigenEBNA-3C, epstein-barr virusEndopeptidasesEpstein-Barr Virus Nuclear Antigensubiquitin-specific peptidase 46, humanUbiquitin ThiolesteraseUSP12 protein, human

Identifiers

PMID25855980
PMCPMC4391933

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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.