Linked Life Data

16267042

Source:http://linkedlifedata.com/resource/pubmed/id/16267042

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
52
pubmed:dateCreated
2005-12-26
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
43272-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16267042-Active Transport, Cell Nucleus, pubmed-meshheading:16267042-Arginine, pubmed-meshheading:16267042-Binding Sites, pubmed-meshheading:16267042-Cell Line, pubmed-meshheading:16267042-Cell Proliferation, pubmed-meshheading:16267042-Cytokines, pubmed-meshheading:16267042-Cytoplasm, pubmed-meshheading:16267042-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:16267042-Enzyme Activation, pubmed-meshheading:16267042-Genetic Vectors, pubmed-meshheading:16267042-Humans, pubmed-meshheading:16267042-I-kappa B Kinase, pubmed-meshheading:16267042-Immunoblotting, pubmed-meshheading:16267042-Inflammation, pubmed-meshheading:16267042-Lysine, pubmed-meshheading:16267042-Mutation, pubmed-meshheading:16267042-Peptides, pubmed-meshheading:16267042-Phenotype, pubmed-meshheading:16267042-Phosphorylation, pubmed-meshheading:16267042-Protein Processing, Post-Translational, pubmed-meshheading:16267042-Protein Structure, Tertiary, pubmed-meshheading:16267042-Serine, pubmed-meshheading:16267042-Signal Transduction, pubmed-meshheading:16267042-Subcellular Fractions, pubmed-meshheading:16267042-Transfection, pubmed-meshheading:16267042-Ubiquitin
pubmed:year
2005
pubmed:articleTitle
Site-specific monoubiquitination of IkappaB kinase IKKbeta regulates its phosphorylation and persistent activation.
pubmed:affiliation
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural