Zhang, X. ; Schuhmachers, P.* ; Mourao, A. ; Giansanti, P.* ; Murer, A.* ; Thumann, S. ; Kuklik-Roos, C. ; Beer, S. ; Hauck, S.M. ; Hammerschmidt, W. ; Kuppers, R.* ; Kuster, B.* ; Raab, M.* ; Strebhardt, K.* ; Sattler, M. ; Münz, C.* ; Kempkes, B.
PLK1-dependent phosphorylation restrains EBNA2 activity and lymphomagenesis in EBV-infected mice.
EMBO Rep.:e53007 (2021)
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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
B-lymphomagenesis ; Ebna2 ; Ebv ; Plk1 ; Humanized Mice; Epstein-barr-virus; Polo-like Kinase; Nuclear-protein-2 Acidic Domain; Box Domain; Physical Interaction; Plk1; Binding; Target; Hyperphosphorylation; Transactivation
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2021
Prepublished im Jahr
HGF-Berichtsjahr
2021
ISSN (print) / ISBN
1469-221X
e-ISSN
1469-3178
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Artikelnummer: e53007
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Verlag
EMBO Press
Verlagsort
111 River St, Hoboken 07030-5774, Nj Usa
Tag d. mündl. Prüfung
0000-00-00
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Prüfer
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0000-00-00
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0000-00-00
Anmelder/Inhaber
weitere Inhaber
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Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30203 - Molecular Targets and Therapies
Forschungsfeld(er)
Immune Response and Infection
Enabling and Novel Technologies
PSP-Element(e)
G-501500-002
G-503000-001
G-501500-001
G-505700-001
Förderungen
Swiss National Science Foundation
Cancer Research Switzerland
China-Scholarship-Council
Copyright
Erfassungsdatum
2021-11-22