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TRIM59 interacts with ECSIT and negatively regulates NF-κB and IRF-3/7-mediated signal pathways
| Title: | TRIM59 interacts with ECSIT and negatively regulates NF-κB and IRF-3/7-mediated signal pathways |
| Authors: | Kondo, Takeshi Browse this author →KAKEN DB | | Watanabe, Masashi Browse this author | | Hatakeyama, Shigetsugu Browse this author →KAKEN DB |
| Keywords: | TRIM59 | | ECSIT | | IPS-1 | | NF-κB | | IRF |
| Issue Date: | 8-Jun-2012 |
| Publisher: | Elsevier |
| Journal Title: | Biochemical and Biophysical Research Communications |
| Volume: | 422 |
| Issue: | 3 |
| Start Page: | 501 |
| End Page: | 507 |
| Publisher DOI: | 10.1016/j.bbrc.2012.05.028 |
| PMID: | 22588174 |
| Abstract: | Innate immune responses are triggered by pathogen-associated molecular patterns (PAMPs) through pattern recognition receptors (PRRs) and then activate intracellular signaling pathways including NF-κB and interferon regulatory factors. Recently, it has been reported that tripartite motif (TRIM) proteins function as crucial regulators via ubiquitin-mediated modifications for these signaling pathways. In this study, we showed that one of the TRIM family ubiquitin ligases, TRIM59, interacts with ECSIT as an adaptor protein required for the TLR-mediated transduction pathway. Luciferase reporter assays using reporter plasmids including NF-κB responsive element, interferon β (IFN-β) promoter and interferon-sensitive response element (ISRE) showed that overexpression of TRIM59 repressed their transcriptional activities, whereas knockdown of TRIM59 enhanced their transcriptional activities. Furthermore, TRIM59 inhibited phosphorylation and dimerization of IRF3 and IRF7, suggesting that TRIM59 negatively regulates upstream kinases for IRFs. These findings indicate that TRIM59 may serve as a multifunctional regulator for innate immune signaling pathways. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/49795 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 畠山 鎮次
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