Source:http://linkedlifedata.com/resource/pubmed/id/15618216
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
9
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pubmed:dateCreated |
2005-2-28
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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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NFKBIZ protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
4
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7444-51
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pubmed:dateRevised |
2008-11-21
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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
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pubmed:year |
2005
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pubmed:articleTitle |
Positive and negative regulation of nuclear factor-kappaB-mediated transcription by IkappaB-zeta, an inducible nuclear protein.
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pubmed:affiliation |
Department of Molecular and Cellular Biochemistry, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
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pubmed:publicationType |
Journal Article
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