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STAP-2 Negatively Regulates both Canonical and Noncanonical NF-κB Activation Induced by Epstein-Barr Virus-Derived Latent Membrane Protein 1
| Title: | STAP-2 Negatively Regulates both Canonical and Noncanonical NF-κB Activation Induced by Epstein-Barr Virus-Derived Latent Membrane Protein 1 |
| Authors: | Ikeda, Osamu Browse this author | | Sekine, Yuichi Browse this author | | Yasui, Teruhito Browse this author | | Oritani, Kenji Browse this author | | Sugiyma, Kenji Browse this author | | Muromoto, Ryuta Browse this author | | Ohbayashi, Norihiko Browse this author | | Yoshimura, Akihiko Browse this author | | Matsuda, Tadashi Browse this author |
| Issue Date: | Aug-2008 |
| Publisher: | American Society for Microbiology |
| Journal Title: | Molecular and Cellular Biology |
| Volume: | 28 |
| Issue: | 16 |
| Start Page: | 5027 |
| End Page: | 5042 |
| Publisher DOI: | 10.1128/MCB.00194-08 |
| 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. |
| Rights: | Copyright © 2008, American Society for Microbiology |
| Type: | article |
| URI: | http://hdl.handle.net/2115/34635 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 松田 正
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