Abstract
Upon activation, NF-kappaB translocates into the nucleus and initiates many biological events. This NF-kappaB signaling is mainly induced by the protein kinase IKK beta. Early in this signaling pathway, IKK beta 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, IKK beta is persistently phosphorylated, which chronically activates NF-kappaB signaling. But the active IKK beta is conjugated with a monoubiquitin by the E3 ubiquitin ligase Ro52, and the IKK beta-induced NF-kappaB 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 IKK beta to autophagosomes. Furthermore, using reporter assays, we show that Ro52 suppresses IKK beta-induced NF-kappaB 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 IKK beta through autophagy.
(c) 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amino Acid Substitution
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Autophagy / physiology*
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Biological Transport, Active
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Cell Line
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Down-Regulation
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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HeLa Cells
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Humans
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I-kappa B Kinase / chemistry
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I-kappa B Kinase / metabolism*
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Luminescent Proteins / genetics
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Luminescent Proteins / metabolism
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Models, Biological
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Mutagenesis, Site-Directed
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NF-kappa B / metabolism
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Nuclear Proteins / chemistry
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Phagosomes / metabolism
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Phosphorylation
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Red Fluorescent Protein
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Ribonucleoproteins / chemistry
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Ribonucleoproteins / genetics
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Ribonucleoproteins / metabolism*
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Signal Transduction
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Ubiquitin-Protein Ligases / chemistry
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Ubiquitin-Protein Ligases / genetics
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Ubiquitin-Protein Ligases / metabolism*
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Ubiquitination
Substances
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DNA-Binding Proteins
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Luminescent Proteins
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NF-kappa B
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Nuclear Proteins
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Recombinant Fusion Proteins
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Ribonucleoproteins
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SS-A antigen
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enhanced green fluorescent protein
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Green Fluorescent Proteins
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Ubiquitin-Protein Ligases
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I-kappa B Kinase