PLK1-dependent phosphorylation restrains EBNA2 activity and lymphomagenesis in EBV-infected mice.
B-lymphomagenesis
EBNA2
EBV
PLK1
humanized mice
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
06 12 2021
06 12 2021
Historique:
revised:
17
08
2021
received:
06
04
2021
accepted:
10
09
2021
pubmed:
5
10
2021
medline:
15
3
2022
entrez:
4
10
2021
Statut:
ppublish
Résumé
While Epstein-Barr virus (EBV) establishes a life-long latent infection in apparently healthy human immunocompetent hosts, immunodeficient individuals are at particular risk to develop lymphoproliferative B-cell malignancies caused by EBV. A key EBV protein is the transcription factor EBV nuclear antigen 2 (EBNA2), which initiates B-cell proliferation. Here, we combine biochemical, cellular, and in vivo experiments demonstrating that the mitotic polo-like kinase 1 (PLK1) binds to EBNA2, phosphorylates its transactivation domain, and thereby inhibits its biological activity. EBNA2 mutants that impair PLK1 binding or prevent EBNA2 phosphorylation are gain-of-function mutants. They exhibit enhanced transactivation capacities, accelerate the proliferation of infected B cells, and promote the development of monoclonal B-cell lymphomas in infected mice. Thus, PLK1 coordinates the activity of EBNA2 to attenuate the risk of tumor incidences in favor of the establishment of latency in the infected but healthy host.
Identifiants
pubmed: 34605140
doi: 10.15252/embr.202153007
pmc: PMC8647151
doi:
Substances chimiques
Cell Cycle Proteins
0
Epstein-Barr Virus Nuclear Antigens
0
Proto-Oncogene Proteins
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e53007Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
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