Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5917864 | Molecular Immunology | 2010 | 10 Pages |
Abstract
Upon activation, NF-κB translocates into the nucleus and initiates many biological events. This NF-κB signaling is mainly induced by the protein kinase IKKβ. Early in this signaling pathway, IKKβ is phosphorylated for activation by several factors, such as pro-inflammatory cytokines and the Tax oncoprotein of human T-cell leukemia virus type 1 (HTLV-1). In cells expressing Tax protein, IKKβ is persistently phosphorylated, which chronically activates NF-κB signaling. But the active IKKβ is conjugated with a monoubiquitin by the E3 ubiquitin ligase Ro52, and the IKKβ-induced NF-κB signaling is downregulated. However, the mechanism of the downregulation has been unknown. Here, we show that Ro52-mediated monoubiquitination is involved in the subcellular translocation of active IKKβ to autophagosomes. Furthermore, using reporter assays, we show that Ro52 suppresses IKKβ-induced NF-κB signaling and that this suppression is blocked by an autophagy inhibitor. These results suggest that Ro52-mediated monoubiquitination plays a critical role in the downregulation of active IKKβ through autophagy.
Keywords
HTLV-1PBSmRFP3-MATNFHEKeGFP3-methyladenineAutophagyinflammationProtein degradationtumor necrosis factorTraffickingPhosphate-buffered salineMonoubiquitinationhemagglutininpolymerase chain reactionPCRHuman T-cell leukemia virus type 1enhanced green fluorescent proteinmonomeric red fluorescent proteinhuman embryonic kidney
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Authors
Motoko Niida, Makoto Tanaka, Tetsu Kamitani,