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

Ikeda, Osamu; Miyasaka, Yuto; Yoshida, Ryuji; Mizushima, Akihiro; Oritani, Kenji; Sekine, Yuichi; Kuroda, Makoto; Yasui, Teruhito; Fujimuro, Masahiro; Muromoto, Ryuta; Nanbo, Asuka; Matsuda, Tadashi

doi:10.1016/j.febslet.2010.01.060

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Volume 584, Issue 5 , Pages 865-872, 5 March 2010

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

Edited by Gianni Cesareni

Osamu Ikeda
- Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Yuto Miyasaka
- Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Ryuji Yoshida
- Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Akihiro Mizushima
- Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Kenji Oritani
- Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
Yuichi Sekine
- Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Makoto Kuroda
- Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Teruhito Yasui
- Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan
Masahiro Fujimuro
- Department of Molecular Cell Biology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo 409-3898, Japan
Ryuta Muromoto
- Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Asuka Nanbo
- Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Tadashi Matsuda
- Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
- Corresponding author. Address: Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku Kita 12 Nishi 6, Sapporo 060-0812, Japan. Fax: +81 11 706 4990.

Received 13 November 2009; received in revised form 13 January 2010; accepted 27 January 2010. published online 05 February 2010.

Abstract

Epstein–Barr virus latent membrane protein 1 (LMP1) activates NF-κB 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-κB 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-κB activation and subsequent IL-6 production. Regarding the mechanisms involved, we found that BS69 directly interacted with TRAF3, a negative regulator of NF-κB activation. Furthermore, small-interfering RNA-mediated knockdown experiments revealed that TRAF3 was involved in the BS69-mediated suppression of LMP1/CTAR1-induced NF-κB 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)

Keywords: BS69, EBV, LMP1, TRAF3, NF-κB, Transcription