Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2005-2-28
pubmed:databankReference
pubmed:abstractText
IkappaB-zeta is an inducible nuclear protein that interacts with nuclear factor-kappaB (NF-kappaB) via its carboxyl-terminal ankyrin-repeats. Previous studies using an NF-kappaB reporter have shown that IkappaB-zeta inhibits the activity of NF-kappaB. In the present study, we dissected the amino-terminal region of IkappaB-zeta, which shows no homology to any other proteins. Indirect immunofluorescence studies demonstrated the presence of a bipartite nuclear localization signal spanning amino acids 163-178. Using GAL4 fusion proteins, we found that internal fragments containing amino acids 329-402 possessed intrinsic transcriptional activation activity. Interestingly, the activity was not detected in GAL4 fusion proteins of the full-length IkappaB-zeta. On the other hand, the GAL4-dependent transcriptional activity was generated by co-expression of the GAL4-NF-kappaB p50 subunit fusion protein and the full-length IkappaB-zeta, neither of which exhibited the activity on their own. A new splicing variant, IkappaB-zeta(D), with a deletion of amino acids 236-429, was found to lack transactivation activity. Forced expression of IkappaB-zeta, but not IkappaB-zeta(D), augmented interleukin-6 production, indicating the functional significance of the transactivation activity. In contrast, tumor necrosis factor-alpha production was inhibited by expression of IkappaB-zeta, highlighting the dual functions of this molecule. These results indicate that IkappaB-zeta harbors latent transcriptional activation activity, and that the activity is expressed upon interaction with the NF-kappaB p50 subunit. In addition to the inhibitory activity on NF-kappaB-mediated transcription, the transcriptional activation activity of IkappaB-zeta should be crucial for the regulation of inflammation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
4
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7444-51
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15618216-Alternative Splicing, pubmed-meshheading:15618216-Animals, pubmed-meshheading:15618216-COS Cells, pubmed-meshheading:15618216-Cell Line, pubmed-meshheading:15618216-Fluorescent Antibody Technique, Indirect, pubmed-meshheading:15618216-Gene Deletion, pubmed-meshheading:15618216-Gene Expression Regulation, pubmed-meshheading:15618216-Genes, Reporter, pubmed-meshheading:15618216-HeLa Cells, pubmed-meshheading:15618216-Humans, pubmed-meshheading:15618216-Immunoblotting, pubmed-meshheading:15618216-Immunoprecipitation, pubmed-meshheading:15618216-Inflammation, pubmed-meshheading:15618216-Interleukin-6, pubmed-meshheading:15618216-Mice, pubmed-meshheading:15618216-Microscopy, Fluorescence, pubmed-meshheading:15618216-Molecular Sequence Data, pubmed-meshheading:15618216-NF-kappa B, pubmed-meshheading:15618216-NIH 3T3 Cells, pubmed-meshheading:15618216-Nuclear Proteins, pubmed-meshheading:15618216-Protein Binding, pubmed-meshheading:15618216-Protein Structure, Tertiary, pubmed-meshheading:15618216-RNA, Messenger, pubmed-meshheading:15618216-Recombinant Fusion Proteins, pubmed-meshheading:15618216-Retroviridae, pubmed-meshheading:15618216-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:15618216-Transcription, Genetic, pubmed-meshheading:15618216-Transcriptional Activation, pubmed-meshheading:15618216-Transfection
pubmed:year
2005
pubmed:articleTitle
Positive and negative regulation of nuclear factor-kappaB-mediated transcription by IkappaB-zeta, an inducible nuclear protein.
pubmed:affiliation
Department of Molecular and Cellular Biochemistry, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
pubmed:publicationType
Journal Article