Evidence map›Paper›PMID 37262099›Full record

ArticlePLoS pathogens2023

Regulation of EBNA1 protein stability and DNA replication activity by PLOD1 lysine hydroxylase.

Jayaraju Dheekollu, Andreas Wiedmer, Samantha S Soldan, Leonardo Josué Castro-Muñoz, Christopher Chen, Hsin-Yao Tang, David W Speicher, Paul M Lieberman

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

12 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Chromatin Control of EBV Infection and Latency.Current topics in microbiology and immunology · 2025
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. 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

8 authors at 1 institution in 1 country.

Jayaraju DheekolluThe Wistar Institute, Philadelphia, Pennsylvania, United States of America.
Andreas WiedmerThe Wistar Institute, Philadelphia, Pennsylvania, United States of America.
Samantha S SoldanThe Wistar Institute, Philadelphia, Pennsylvania, United States of America.
Leonardo Josué Castro-MuñozThe Wistar Institute, Philadelphia, Pennsylvania, United States of America.
Christopher ChenThe Wistar Institute, Philadelphia, Pennsylvania, United States of America.
Hsin-Yao TangThe Wistar Institute, Philadelphia, Pennsylvania, United States of America.
David W SpeicherThe Wistar Institute, Philadelphia, Pennsylvania, United States of America.
Paul M LiebermanThe Wistar Institute, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0002-3935-9921
The Wistar Institute · US

Funding

Tumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Aaron Robert Goldman · 1985 to 2026
$75.9M
TRAINING PROGRAM IN BASIC CANCER RESEARCHT32CA009171 · NCI · WISTAR INSTITUTE · PI Alessandro Gardini · 1985 to 2026
$15.3M
Targeting the Epigenetic and Metabolic Control of EBV-Epithelial CancersP01CA269043 · NCI · WISTAR INSTITUTE · PI Italo Tempera · 2023 to 2026
$12.0M
Regulation of Epstein-Barr Virus LatencyR01CA093606 · NCI · WISTAR INSTITUTE · PI LIEBERMAN, PAUL M. · 2002 to 2022
$6.7M
Epigenetic Regulation of Epstein-Barr Virus Latency ProgramsR01DE017336 · NIDCR · WISTAR INSTITUTE · PI PAUL M. LIEBERMAN · 2005 to 2026
$6.5M
Role of TERRA in Telomere Maintenance and Telomere Stress ResponseR01CA140652 · NCI · WISTAR INSTITUTE · PI LIEBERMAN, PAUL M. · 2010 to 2025
$6.0M
Regulation of EBV Latency by Purine Metabolism and SignalingR01AI153508 · NIAID · WISTAR INSTITUTE · PI TEMPERA, ITALO · 2021 to 2025
$2.3M
Advancing Cancer Research through Comprehensive Proteomics and Metabolomics AnalysesR50CA221838 · NCI · WISTAR INSTITUTE · PI Hsin-Yao Tang · 2017 to 2026
$2.1M
Unique Genomic Regions of Y pestis in PathogenesisR21AI053508 · NIAID · UNIVERSITY OF CALIF-LAWRNC LVRMR NAT LAB · PI GARCIA, EMILIO · 2002 to 2003
$529k
NCI NIH HHS P01 CA269043NCI NIH HHS P30 CA010815NCI NIH HHS R01 CA093606NCI NIH HHS R01 CA140652NCI NIH HHS R50 CA221838NCI NIH HHS T32 CA009171NIAID NIH HHS R01 AI153508NIAID NIH HHS R21 AI053508NIDCR NIH HHS R01 DE017336
6 · The paper itself

Abstract

Epstein-Barr virus (EBV) is a ubiquitous human γ-herpesvirus that is causally associated with various malignancies and autoimmune disease. Epstein-Barr Nuclear Antigen 1 (EBNA1) is the viral-encoded DNA binding protein required for viral episome maintenance and DNA replication during latent infection in proliferating cells. EBNA1 is known to be a highly stable protein, but the mechanisms regulating protein stability and how this may be linked to EBNA1 function is not fully understood. Proteomic analysis of EBNA1 revealed interaction with Procollagen Lysine-2 Oxoglutarate 5 Dioxygenase (PLOD) family of proteins. Depletion of PLOD1 by shRNA or inhibition with small molecule inhibitors 2,-2' dipyridyl resulted in the loss of EBNA1 protein levels, along with a selective growth inhibition of EBV-positive lymphoid cells. PLOD1 depletion also caused a loss of EBV episomes from latently infected cells and inhibited oriP-dependent DNA replication. Mass spectrometry identified EBNA1 peptides with lysine hydroxylation at K460 or K461. Mutation of K460, but not K461 abrogates EBNA1-driven DNA replication of oriP, but did not significantly affect EBNA1 DNA binding. Mutations in both K460 and K461 perturbed interactions with PLOD1, as well as decreased EBNA1 protein stability. These findings suggest that PLOD1 is a novel interaction partner of EBNA1 that regulates EBNA1 protein stability and function in viral plasmid replication, episome maintenance and host cell survival.

Indexed as

Epstein-Barr Virus InfectionsProcollagen-Lysine, 2-Oxoglutarate 5-DioxygenaseDNA ReplicationEpstein-Barr Virus Nuclear AntigensHerpesvirus 4, HumanHumansLysinePlasmidsProtein StabilityProteomicsReplication OriginVirus ReplicationEBV-encoded nuclear antigen 1Epstein-Barr Virus Nuclear AntigensLysinePLOD1 protein, humanProcollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase

Identifiers

PMID37262099
PMCPMC10263308
OpenAlexW4379054351

What OpenQuestion holds

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LicenceCC BY
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.