| pubmed-article:17244613 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:17244613 | lifeskim:mentions | umls-concept:C1523116 | lld:lifeskim |
| pubmed-article:17244613 | lifeskim:mentions | umls-concept:C1546856 | lld:lifeskim |
| pubmed-article:17244613 | pubmed:issue | 12 | lld:pubmed |
| pubmed-article:17244613 | pubmed:dateCreated | 2007-3-19 | lld:pubmed |
| pubmed-article:17244613 | pubmed:abstractText | Activation of NF-kappaB by the pro-inflammatory cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1) requires the IkappaB kinase (IKK) complex, which contains two kinases named IKKalpha and IKKbeta and a critical regulatory subunit named NEMO. Although we have previously demonstrated that NEMO associates with both IKKs, genetic studies reveal that only its interaction with IKKbeta is required for TNF-induced NF-kappaB activation. To determine whether NEMO and IKKalpha can form a functional IKK complex capable of activating the classical NF-kappaB pathway in the absence of IKKbeta, we utilized a panel of mouse embryonic fibroblasts (MEFs) lacking each of the IKK complex subunits. This confirmed that TNF-induced IkappaBalpha degradation absolutely requires NEMO and IKKbeta. In contrast, we consistently observed intact IkappaBalpha degradation and NF-kappaB activation in response to IL-1 in two separate cell lines lacking IKKbeta. Furthermore, exogenously expressed, catalytically inactive IKKbeta blocked TNF- but not IL-1-induced IkappaBalpha degradation in wild-type MEFs, and reconstitution of IKKalpha/beta double knockout cells with IKKalpha rescued IL-1- but not TNF-induced NF-kappaB activation. Finally, we have shown that incubation of IKKbeta-deficient MEFs with a cell-permeable peptide that blocks the interaction of NEMO with the IKKs inhibits IL-1-induced NF-kappaB activation. Our results therefore demonstrate that NEMO and IKKalpha can form a functional IKK complex that activates the classical NF-kappaB pathway in response to IL-1 but not TNF. These findings further suggest NEMO differentially regulates the fidelity of the IKK subunits activated by distinct upstream signaling pathways. | lld:pubmed |
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| pubmed-article:17244613 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:17244613 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:17244613 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:17244613 | pubmed:month | Mar | lld:pubmed |
| pubmed-article:17244613 | pubmed:issn | 0021-9258 | lld:pubmed |
| pubmed-article:17244613 | pubmed:author | pubmed-author:SoltLaura ALA | lld:pubmed |
| pubmed-article:17244613 | pubmed:author | pubmed-author:MayMichael... | lld:pubmed |
| pubmed-article:17244613 | pubmed:author | pubmed-author:OrangeJordan... | lld:pubmed |
| pubmed-article:17244613 | pubmed:author | pubmed-author:MadgeLisa ALA | lld:pubmed |
| pubmed-article:17244613 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:17244613 | pubmed:day | 23 | lld:pubmed |
| pubmed-article:17244613 | pubmed:volume | 282 | lld:pubmed |
| pubmed-article:17244613 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:17244613 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:17244613 | pubmed:pagination | 8724-33 | lld:pubmed |
| pubmed-article:17244613 | pubmed:dateRevised | 2011-9-26 | lld:pubmed |
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| pubmed-article:17244613 | pubmed:year | 2007 | lld:pubmed |
| pubmed-article:17244613 | pubmed:articleTitle | Interleukin-1-induced NF-kappaB activation is NEMO-dependent but does not require IKKbeta. | lld:pubmed |
| pubmed-article:17244613 | pubmed:affiliation | Department of Animal Biology, University of Pennsylvania School of Veterinary Medicine, PA 19104, USA. | lld:pubmed |
| pubmed-article:17244613 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:17244613 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
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