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

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)5027-5042
Number of pages16
JournalMolecular and Cellular Biology
Volume28
Issue number16
DOIs
Publication statusPublished - 2008 Aug
Externally publishedYes

Fingerprint

Signal Transducing Adaptor Proteins
Human Herpesvirus 4
Membrane Proteins
B-Lymphocytes
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Tumor Necrosis Factor Receptors
Growth
Proline
Knockout Mice

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

STAP-2 negatively regulates both canonical and noncanonical NF-κB activation induced by Epstein-Barr virus-derived latent membrane protein. / Ikeda, Osamu; Sekine, Yuichi; Yasui, Teruhito; Oritani, Kenji; Sugiyma, Kenji; Muromoto, Ryuta; Ohbayashi, Norihiko; Yoshimura, Akihiko; Matsuda, Tadashi.

In: Molecular and Cellular Biology, Vol. 28, No. 16, 08.2008, p. 5027-5042.

Research output: Contribution to journalArticle

Ikeda, Osamu ; Sekine, Yuichi ; Yasui, Teruhito ; Oritani, Kenji ; Sugiyma, Kenji ; Muromoto, Ryuta ; Ohbayashi, Norihiko ; Yoshimura, Akihiko ; Matsuda, Tadashi. / STAP-2 negatively regulates both canonical and noncanonical NF-κB activation induced by Epstein-Barr virus-derived latent membrane protein. In: Molecular and Cellular Biology. 2008 ; Vol. 28, No. 16. pp. 5027-5042.
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