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Giehler, F. ; Ostertag, M.S. ; Sommermann, T.* ; Weidl, D.* ; Sterz, K. ; Kutz, H. ; Moosmann, A. ; Feller, S.M.* ; Geerlof, A. ; Biesinger, B.* ; Popowicz, G.M. ; Kirchmair, J.* ; Kieser, A.

Epstein-Barr virus-driven B cell lymphoma mediated by a direct LMP1-TRAF6 complex.

Nat. Commun. 15:414 (2024)
DOI PMC
Creative Commons Lizenzvertrag
Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) drives viral B cell transformation and oncogenesis. LMP1’s transforming activity depends on its C-terminal activation region 2 (CTAR2), which induces NF-κB and JNK by engaging TNF receptor-associated factor 6 (TRAF6). The mechanism of TRAF6 recruitment to LMP1 and its role in LMP1 signalling remains elusive. Here we demonstrate that TRAF6 interacts directly with a viral TRAF6 binding motif within CTAR2. Functional and NMR studies supported by molecular modeling provide insight into the architecture of the LMP1-TRAF6 complex, which differs from that of CD40-TRAF6. The direct recruitment of TRAF6 to LMP1 is essential for NF-κB activation by CTAR2 and the survival of LMP1-driven lymphoma. Disruption of the LMP1-TRAF6 complex by inhibitory peptides interferes with the survival of EBV-transformed B cells. In this work, we identify LMP1-TRAF6 as a critical virus-host interface and validate this interaction as a potential therapeutic target in EBV-associated cancer.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Nf-kappa-b; Membrane-protein 1; Receptor-associated Factor-3; Terminal Kinase Pathway; Latent Membrane-protein-1; Binding-site; Traf-binding; Growth Transformation; Signal-transduction; Critical Regulator
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 15, Heft: 1, Seiten: , Artikelnummer: 414 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Signaling and Translation (SAT)
Institute of Structural Biology (STB)
Research Unit Gene Vector (AGV)
Förderungen Deutsches Zentrum für Infektionsforschung (German Center for Infection Research)
Deutsche Forschungsgemeinschaft (German Research Foundation)