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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5484
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pubmed:dateCreated |
2000-9-14
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pubmed:abstractText |
Activation of the transcription factor nuclear factor (NF)-kappaB by proinflammatory stimuli leads to increased expression of genes involved in inflammation. Activation of NF-kappaB requires the activity of an inhibitor of kappaB (IkappaB)-kinase (IKK) complex containing two kinases (IKKalpha and IKKbeta) and the regulatory protein NEMO (NF-kappaB essential modifier). An amino-terminal alpha-helical region of NEMO associated with a carboxyl-terminal segment of IKKalpha and IKKbeta that we term the NEMO-binding domain (NBD). A cell-permeable NBD peptide blocked association of NEMO with the IKK complex and inhibited cytokine-induced NF-kappaB activation and NF-kappaB-dependent gene expression. The peptide also ameliorated inflammatory responses in two experimental mouse models of acute inflammation. The NBD provides a target for the development of drugs that would block proinflammatory activation of the IKK complex without inhibiting basal NF-kappaB activity.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents...,
http://linkedlifedata.com/resource/pubmed/chemical/CHUK protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Chuk protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/E-Selectin,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/IKBKB protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/IKBKE protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ikbkb protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ikbke protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0036-8075
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
289
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1550-4
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10968790-Amino Acid Sequence,
pubmed-meshheading:10968790-Animals,
pubmed-meshheading:10968790-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:10968790-COS Cells,
pubmed-meshheading:10968790-Cells, Cultured,
pubmed-meshheading:10968790-E-Selectin,
pubmed-meshheading:10968790-Endothelium, Vascular,
pubmed-meshheading:10968790-Gene Expression Regulation,
pubmed-meshheading:10968790-HeLa Cells,
pubmed-meshheading:10968790-Humans,
pubmed-meshheading:10968790-I-kappa B Kinase,
pubmed-meshheading:10968790-Inflammation,
pubmed-meshheading:10968790-Mice,
pubmed-meshheading:10968790-Mice, Inbred C57BL,
pubmed-meshheading:10968790-Molecular Sequence Data,
pubmed-meshheading:10968790-Mutation,
pubmed-meshheading:10968790-NF-kappa B,
pubmed-meshheading:10968790-Peptides,
pubmed-meshheading:10968790-Point Mutation,
pubmed-meshheading:10968790-Protein Structure, Tertiary,
pubmed-meshheading:10968790-Protein-Serine-Threonine Kinases,
pubmed-meshheading:10968790-Recombinant Fusion Proteins
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pubmed:year |
2000
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pubmed:articleTitle |
Selective inhibition of NF-kappaB activation by a peptide that blocks the interaction of NEMO with the IkappaB kinase complex.
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pubmed:affiliation |
Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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