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http://purl.uniprot.org/citations/16267042http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16267042http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16267042http://www.w3.org/2000/01/rdf-schema#comment"Transcription factor NF-kappaB governs the expression of multiple genes involved in cell growth, immunity, and inflammation. Nuclear translocation of NF-kappaB is regulated from the cytoplasm by IkappaB kinase-beta (IKKbeta), which earmarks inhibitors of NF-kappaB for polyubiquination and proteasome-mediated degradation. Activation of IKKbeta is contingent upon signal-induced phosphorylation of its T loop at Ser-177/Ser-181. T loop phosphorylation also renders IKKbeta a substrate for monoubiquitination in cells exposed to chronic activating cues, such as the Tax oncoprotein or sustained signaling through proinflammatory cytokine receptors. Here we provide evidence that the T loop-proximal residue Lys-163 in IKKbeta serves as a major site for signal-induced monoubiquitination with significant regulatory potential. Conservative replacement of Lys-163 with Arg yielded a monoubiquitination-defective mutant of IKKbeta that retains kinase activity in Tax-expressing cells but is impaired for activation mediated by chronic signaling from the type 1 receptor for tumor necrosis factor-alpha. Phosphopeptide mapping experiments revealed that the Lys-163 --> Arg mutation also interferes with proper in vivo but not in vitro phosphorylation of cytokine-responsive serine residues located in the distal C-terminal region of IKKbeta. Taken together, these data indicate that chronic phosphorylation of IKKbeta at Ser-177/Ser-181 leads to monoubiquitin attachment at nearby Lys-163, which in turn modulates the phosphorylation status of IKKbeta at select C-terminal serines. This mechanism for post-translational cross-talk may play an important role in the control of IKKbeta signaling during chronic inflammation."xsd:string
http://purl.uniprot.org/citations/16267042http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m508656200"xsd:string
http://purl.uniprot.org/citations/16267042http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m508656200"xsd:string
http://purl.uniprot.org/citations/16267042http://purl.uniprot.org/core/author"Oltz E.M."xsd:string
http://purl.uniprot.org/citations/16267042http://purl.uniprot.org/core/author"Oltz E.M."xsd:string
http://purl.uniprot.org/citations/16267042http://purl.uniprot.org/core/author"Ballard D.W."xsd:string
http://purl.uniprot.org/citations/16267042http://purl.uniprot.org/core/author"Ballard D.W."xsd:string
http://purl.uniprot.org/citations/16267042http://purl.uniprot.org/core/author"Carter R.S."xsd:string
http://purl.uniprot.org/citations/16267042http://purl.uniprot.org/core/author"Carter R.S."xsd:string
http://purl.uniprot.org/citations/16267042http://purl.uniprot.org/core/author"Arrate P."xsd:string
http://purl.uniprot.org/citations/16267042http://purl.uniprot.org/core/author"Arrate P."xsd:string
http://purl.uniprot.org/citations/16267042http://purl.uniprot.org/core/author"Pennington K.N."xsd:string
http://purl.uniprot.org/citations/16267042http://purl.uniprot.org/core/author"Pennington K.N."xsd:string
http://purl.uniprot.org/citations/16267042http://purl.uniprot.org/core/date"2005"xsd:gYear
http://purl.uniprot.org/citations/16267042http://purl.uniprot.org/core/date"2005"xsd:gYear
http://purl.uniprot.org/citations/16267042http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/16267042http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/16267042http://purl.uniprot.org/core/pages"43272-43279"xsd:string
http://purl.uniprot.org/citations/16267042http://purl.uniprot.org/core/pages"43272-43279"xsd:string
http://purl.uniprot.org/citations/16267042http://purl.uniprot.org/core/title"Site-specific monoubiquitination of IkappaB kinase IKKbeta regulates its phosphorylation and persistent activation."xsd:string
http://purl.uniprot.org/citations/16267042http://purl.uniprot.org/core/title"Site-specific monoubiquitination of IkappaB kinase IKKbeta regulates its phosphorylation and persistent activation."xsd:string
http://purl.uniprot.org/citations/16267042http://purl.uniprot.org/core/volume"280"xsd:string
http://purl.uniprot.org/citations/16267042http://purl.uniprot.org/core/volume"280"xsd:string