ワダ ケイジ
和田 圭司 所属 その他 その他 職種 嘱託医師 |
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論文種別 | 原著 |
言語種別 | 英語 |
査読の有無 | 査読あり |
表題 | Ro52-mediated monoubiquitination of IKK{beta} down-regulates NF-{kappa}B signalling. |
掲載誌名 | 正式名:Journal of biochemistry 略 称:J Biochem ISSNコード:(1756-2651)0021-924X(Linking) |
掲載区分 | 国外 |
巻・号・頁 | 146(6),pp.821-32 |
著者・共著者 | Wada Keiji, Niida Motoko, Tanaka Makoto, Kamitani Tetsu |
発行年月 | 2009/12 |
概要 | Upon activation, NF-kappaB translocates into the nucleus and initiates biological events. This NF-kappaB signalling is mainly regulated by the protein kinase IKKbeta. Early in this signalling pathway, IKKbeta is phosphorylated for activation by several factors, such as pro-inflammatory cytokines and the Tax oncoprotein of HTLV-1. In cells infected by HTLV-1, IKKbeta is persistently phosphorylated and conjugated with monoubiquitin due to Tax expression. Although this Tax-induced monoubiquitination appears to be an important regulation system for IKKbeta, how the monoubiquitination occurs is unknown and its role in NF-kappaB signalling is still unclear. Here, we show that an E3-ubiquitin ligase Ro52 interacts weakly with wild-type IKKbeta but strongly with a phosphomimetic mutant IKKbeta to conjugate monoubiquitin in cooperation with an E2-ubiquitin-conjugating enzyme UbcH5B. These results suggest that the Tax-induced phosphorylation of IKKbeta causes an interaction with Ro52 for the subsequent monoubiquitination. NF-kappaB reporter assays have shown that the IKKbeta activity is suppressed by wild-type Ro52, but not by its inactive mutant. In addition, monoubiquitin fusion of IKKbeta reduced its activity for NF-kappaB signalling. We also found that Ro52 dramatically reduces the level of Tax. These results suggest that Ro52 down-regulates Tax-induced NF-kappaB signalling by monoubiquitinating IKKbeta and by reducing the level of Tax. |
DOI | 10.1093/jb/mvp127 |
PMID | 19675099 |