和田 圭司
Department Other, Other Position |
|
Article types | Original article |
Language | English |
Peer review | Peer reviewed |
Title | Ro52-mediated monoubiquitination of IKK{beta} down-regulates NF-{kappa}B signalling. |
Journal | Formal name:Journal of biochemistry Abbreviation:J Biochem ISSN code:(1756-2651)0021-924X(Linking) |
Domestic / Foregin | Foregin |
Volume, Issue, Page | 146(6),pp.821-32 |
Author and coauthor | Wada Keiji, Niida Motoko, Tanaka Makoto, Kamitani Tetsu |
Publication date | 2009/12 |
Summary | 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 |