BS69 negatively regulates the canonical NF-κB activation induced by Epstein–Barr virus-derived LMP1

Ikeda, Osamu; Sekine, Yuichi; Mizushima, Akihiro; Oritani, Kenji; Yasui, Teruhito; Fujimuro, Masahiro; Muromoto, Ryuta; Nanbo, Asuka; Matsuda, Tadashi

doi:10.1016/j.febslet.2009.04.022

« Previous Next »FEBS Letters
Volume 583, Issue 10 , Pages 1567-1574, 19 May 2009

BS69 negatively regulates the canonical NF-κB activation induced by Epstein–Barr virus-derived LMP1

Edited by Giulio Superti-Furga

Osamu Ikeda
- Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku Kita 12 Nishi 6, Sapporo 060-0812, Japan
Yuichi Sekine
- Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku Kita 12 Nishi 6, Sapporo 060-0812, Japan
Akihiro Mizushima
- Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku Kita 12 Nishi 6, 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
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, Kita-Ku Kita 12 Nishi 6, Sapporo 060-0812, Japan
Asuka Nanbo
- Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku Kita 12 Nishi 6, Sapporo 060-0812, Japan
Tadashi Matsuda
- Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku Kita 12 Nishi 6, Sapporo 060-0812, Japan
- Corresponding author. Fax: +81 11 706 4990.

Received 26 January 2009; received in revised form 2 April 2009; accepted 9 April 2009. published online 20 April 2009.

Abstract

Epstein–Barr virus (EBV) latent membrane protein 1 (LMP1) activates NF-κB signaling pathways through the two C-terminal regions, CTAR1 and CTAR2. BS69 has previously been shown to be involved in LMP1-induced c-Jun N-terminal kinase activation through CTAR2 by interacting with tumor necrosis factor (TNFR) receptor-associated factor 6. In the present study, our manipulation of BS69 expression clearly indicates that BS69 negatively regulates LMP1-mediated NF-κB activation and up-regulates IL-6 mRNA expression and IκB degradation. Our immunoprecipitation experiments suggest that BS69 decreases complex formation between LMP1 and TNFR-associated death domain protein (TRADD).

Structured summary

MINT-7032462: LMP1 (uniprotkb:P03230) physically interacts (MI:0218) with TRADD (uniprotkb:Q15628) by anti bait coimmunoprecipitation (MI:0006)

MINT-7032451: BS69 (uniprotkb:Q15326) and LMP1 (uniprotkb:P03230) colocalize (MI:0403) by fluorescence microscopy (MI:0416)

MINT-7032478: LMP1 (uniprotkb:P03230) physically interacts (MI:0218) with BRAM1 (uniprotkb:Q15326) by anti bait coimmunoprecipitation (MI:0006)

Keywords: Epstein–Barr virus, Latent membrane protein 1, BS69, NF-κB, TNFR-associated death domain protein