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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)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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
Korrespondenzautor
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
ISSN (print) / ISBN 1469-221X
e-ISSN 1469-3178
Zeitschrift EMBO Reports
Quellenangaben Band: , Heft: , Seiten: , Artikelnummer: e53007 Supplement: ,
Verlag EMBO Press
Verlagsort 111 River St, Hoboken 07030-5774, Nj Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Gene Vector (AGV)
Institute of Structural Biology (STB)
CF Metabolomics & Proteomics (CF-MPC)
Förderungen Swiss National Science Foundation
Cancer Research Switzerland
China-Scholarship-Council