BS69 cooperates with TRAF3 in the regulation of Epstein-Barr virus-derived LMP1/CTAR1-induced NF-kappaB activation.
Epstein-Barr virus latent membrane protein 1 (LMP1) activates NF-kappaB 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-kappaB 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-kappaB activation and subsequent IL-6 production. Regarding the mechanisms involved, we found that BS69 directly interacted with TRAF3, a negative regulator of NF-kappaB activation. Furthermore, small-interfering RNA-mediated knockdown experiments revealed that TRAF3 was involved in the BS69-mediated suppression of LMP1/CTAR1-induced NF-kappaB activation.
Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Osamu
O
Ikeda
Yuto
Y
Miyasaka
Ryuji
R
Yoshida
Akihiro
A
Mizushima
Kenji
K
Oritani
Yuichi
Y
Sekine
Makoto
M
Kuroda
Teruhito
T
Yasui
Masahiro
M
Fujimuro
Ryuta
R
Muromoto
Asuka
A
Nanbo
Tadashi
T
Matsuda
D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002460:Cell Line; D045744:Cell Line, Tumor; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D015850:Interleukin-6 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D048008:TNF Receptor-Associated Factor 3 / Q000235:genetics / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D015850:Interleukin-6; D016328:NF-kappa B; D034741:RNA, Small Interfering; D048008:TNF Receptor-Associated Factor 3; D014763:Viral Matrix Proteins; C094763:ZMYND11 protein, human