BS69 cooperates with TRAF3 in the regulation of Epstein-Barr virus-derived LMP1/CTAR1-induced NF-κB activation

Epstein-Barr virus latent membrane protein 1 (LMP1) activates NF-kappa B signaling pathways through two C-terminal regions, CTAR1 and CTAR2. Previous studies have demonstrated that BS69, a multidomain cellular protein, regulates LMP1/CTAR2-mediated NF-kappa B activation by interfering with the complex formation between TRADD and LMP1/CTAR2. Here, we found that BS69 directly interacted with the LMP1/CTAR1 domain and regulated LMP1/CTAR1-mediated NF-kappa B activation and subsequent IL-6 production. Regarding the mechanisms involved, we found that BS69 directly interacted with TRAF3, a negative regulator of NF-kappa B activation. Furthermore, small-interfering RNA-mediated knockdown experiments revealed that TRAF3 was involved in the BS69-mediated suppression of LMP1/CTAR1-induced NF-kappa B activation. Structured summary: MINT-7556591: lmp1 (uniprotkb: P03230) physically interacts (MI:0915) with BS69 (uniprotkb:Q15326) by anti tag coimmunoprecipitation (MI: 0007) MINT-7556646: TRAF6 (uniprotkb:Q9Y4K3) physically interacts (MI: 0915) with BS69 (uniprotkb: Q15326) by anti tag coimmunoprecipitation (MI: 0007) MINT-7556658, MINT-7556670: TRAF3 (uniprotkb:Q13114) physically interacts (MI: 0915) with BS69 (uniprotkb: Q15326) by anti tag coimmunoprecipitation (MI: 0007) MINT-7556607: TRAF1 (uniprotkb:Q13077) physically interacts (MI: 0915) with BS69 (uniprotkb: Q15326) by anti tag coimmunoprecipitation (MI: 0007) MINT-7556634: TRAF5 (uniprotkb:O00463) physically interacts (MI: 0915) with BS69 (uniprotkb: Q15326) by anti tag coimmunoprecipitation (MI: 0007) MINT-7556622: TRAF2 (uniprotkb:Q12933) physically interacts (MI: 0915) with BS69 (uniprotkb: Q15326) by anti tag coimmunoprecipitation (MI: 0007) (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.