STAP-2 negatively regulates both canonical and noncanonical NF-κB activation induced by Epstein-Barr virus-derived latent membrane protein

Osamu Ikeda, Yuichi Sekine, Teruhito Yasui, Kenji Oritani, Kenji Sugiyma, Ryuta Muromoto, Norihiko Ohbayashi, Akihiko Yoshimura, Tadashi Matsuda

研究成果: Article査読

27 被引用数 (Scopus)

抄録

The signal-transducing adaptor protein 2 (STAP-2) is a recently identified adaptor protein that contains a pleckstrin homology (PH) and Src homology 2 (SH2)-like domains, as well as a proline-rich domain in its C-terminal region. In previous studies, we demonstrated that STAP-2 binds to MyD88 and IKK-α or IKK-β and modulates NF-κB signaling in macrophages. In the present study, we found that ectopic expression of STAP-2 inhibited Epstein-Barr virus (EBV) LMP1-mediated NF-κB signaling and interleukin-6 expression. Indeed, STAP-2 associated with LMP1 through its PH and SH2-like domains, and these proteins interacted with each other in EBV-positive human B cells. We found, furthermore, that STAP-2 regulated LMP1-mediated NF-κB signaling through direct or indirect interactions with the tumor necrosis factor receptor (TNFR)-associated factor 3 (TRAF3) and TNFR-associated death domain (TRADD) proteins. STAP-2 mRNA was induced by the expression of LMP1 in human B cells. Furthermore, transient expression of STAP-2 in EBV-positive human B cells decreased cell growth. Finally, STAP-2 knockout mouse embryonic fibroblasts showed enhanced LMP1-induced cell growth. These results suggest that STAP-2 acts as an endogenous negative regulator of EBV LMP1-mediated signaling through TRAF3 and TRADD.

本文言語English
ページ(範囲)5027-5042
ページ数16
ジャーナルMolecular and cellular biology
28
16
DOI
出版ステータスPublished - 2008 8
外部発表はい

ASJC Scopus subject areas

  • 分子生物学
  • 細胞生物学

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