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| Item Type: | Article |
|---|---|
| Title: | Epstein-Barr virus-driven B cell lymphoma mediated by a direct LMP1-TRAF6 complex |
| Creators Name: | Giehler, F., Ostertag, M.S., Sommermann, T., Weidl, D., Sterz, K.R., Kutz, H., Moosmann, A., Feller, S.M., Geerlof, A., Biesinger, B., Popowicz, G.M., Kirchmair, J. and Kieser, A. |
| Abstract: | 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. |
| Keywords: | B-Cell Lymphoma, Epstein-Barr Virus Infections, Human Herpesvirus 4, NF-kappa B, Neoplastic Cell Transformation, TNF Receptor-Associated Factor 6, Viral Cell Transformation, Animals, Mice |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 15 |
| Number: | 1 |
| Page Range: | 414 |
| Date: | 10 January 2024 |
| Official Publication: | https://doi.org/10.1038/s41467-023-44455-w |
| PubMed: | View item in PubMed |
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