| pubmed-article:18272581 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:18272581 | lifeskim:mentions | umls-concept:C0031715 | lld:lifeskim |
| pubmed-article:18272581 | lifeskim:mentions | umls-concept:C0376525 | lld:lifeskim |
| pubmed-article:18272581 | lifeskim:mentions | umls-concept:C0424295 | lld:lifeskim |
| pubmed-article:18272581 | lifeskim:mentions | umls-concept:C0036720 | lld:lifeskim |
| pubmed-article:18272581 | lifeskim:mentions | umls-concept:C0004083 | lld:lifeskim |
| pubmed-article:18272581 | lifeskim:mentions | umls-concept:C0376315 | lld:lifeskim |
| pubmed-article:18272581 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:18272581 | lifeskim:mentions | umls-concept:C0301039 | lld:lifeskim |
| pubmed-article:18272581 | pubmed:issue | 8 | lld:pubmed |
| pubmed-article:18272581 | pubmed:dateCreated | 2008-3-26 | lld:pubmed |
| pubmed-article:18272581 | pubmed:abstractText | The IkappaB kinase-related kinases, TBK1 and IKKi, were recently shown to be responsible for the C-terminal phosphorylation of IRF-3. However, the identity of the phosphoacceptor site(s) targeted by these two kinases remains unclear. Using a biological assay based on the IRF-3-mediated production of antiviral cytokines, we demonstrate here that all Ser/Thr clusters of IRF-3 are required for its optimal transactivation capacity. In vitro kinase assays using full-length His-IRF-3 as a substrate combined with mass spectrometry analysis revealed that serine 402 and serine 396 are directly targeted by TBK1. Analysis of Ser/Thr-to-Ala mutants revealed that the S396A mutation, located in cluster II, abolished IRF-3 homodimerization, CBP association, and nuclear accumulation. However, production of antiviral cytokines was still present in IRF-3 S396A-expressing cells. Interestingly, mutation of serine 339, which is involved in IRF-3 stability, also abrogated CBP association and dimerization without affecting gene transactivation as long as serine 396 remained available for phosphorylation. Complementation of IRF-3-knockout mouse embryonic fibroblasts also revealed a compensatory mechanism of serine 339 and serine 396 in the ability of IRF-3 to induce expression of the interferon-stimulated genes ISG56 and ISG54. These data lead us to reconsider the current model of IRF-3 activation. We propose that conventional biochemical assays used to measure IRF-3 activation are not sensitive enough to detect the small fraction of IRF-3 needed to elicit a biological response. Importantly, our study establishes a molecular link between the role of serine 339 in IRF-3 homodimerization, CBP association, and its destabilization. | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:language | eng | lld:pubmed |
| pubmed-article:18272581 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:18272581 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18272581 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:18272581 | pubmed:month | Apr | lld:pubmed |
| pubmed-article:18272581 | pubmed:issn | 1098-5514 | lld:pubmed |
| pubmed-article:18272581 | pubmed:author | pubmed-author:ServantMarc... | lld:pubmed |
| pubmed-article:18272581 | pubmed:author | pubmed-author:GrandvauxNath... | lld:pubmed |
| pubmed-article:18272581 | pubmed:author | pubmed-author:MelocheSylvai... | lld:pubmed |
| pubmed-article:18272581 | pubmed:author | pubmed-author:BonneilEricE | lld:pubmed |
| pubmed-article:18272581 | pubmed:author | pubmed-author:ThibaultPierr... | lld:pubmed |
| pubmed-article:18272581 | pubmed:author | pubmed-author:ClémentJean-F... | lld:pubmed |
| pubmed-article:18272581 | pubmed:author | pubmed-author:GravelSimon-P... | lld:pubmed |
| pubmed-article:18272581 | pubmed:author | pubmed-author:Bibeau-Poirie... | lld:pubmed |
| pubmed-article:18272581 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:18272581 | pubmed:volume | 82 | lld:pubmed |
| pubmed-article:18272581 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:18272581 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:18272581 | pubmed:pagination | 3984-96 | lld:pubmed |
| pubmed-article:18272581 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |
| pubmed-article:18272581 | pubmed:meshHeading | pubmed-meshheading:18272581... | lld:pubmed |
| pubmed-article:18272581 | pubmed:meshHeading | pubmed-meshheading:18272581... | lld:pubmed |
| pubmed-article:18272581 | pubmed:meshHeading | pubmed-meshheading:18272581... | lld:pubmed |
| pubmed-article:18272581 | pubmed:meshHeading | pubmed-meshheading:18272581... | lld:pubmed |
| pubmed-article:18272581 | pubmed:meshHeading | pubmed-meshheading:18272581... | lld:pubmed |
| pubmed-article:18272581 | pubmed:meshHeading | pubmed-meshheading:18272581... | lld:pubmed |
| pubmed-article:18272581 | pubmed:meshHeading | pubmed-meshheading:18272581... | lld:pubmed |
| pubmed-article:18272581 | pubmed:meshHeading | pubmed-meshheading:18272581... | lld:pubmed |
| pubmed-article:18272581 | pubmed:meshHeading | pubmed-meshheading:18272581... | lld:pubmed |
| pubmed-article:18272581 | pubmed:meshHeading | pubmed-meshheading:18272581... | lld:pubmed |
| pubmed-article:18272581 | pubmed:meshHeading | pubmed-meshheading:18272581... | lld:pubmed |
| pubmed-article:18272581 | pubmed:meshHeading | pubmed-meshheading:18272581... | lld:pubmed |
| pubmed-article:18272581 | pubmed:meshHeading | pubmed-meshheading:18272581... | lld:pubmed |
| pubmed-article:18272581 | pubmed:meshHeading | pubmed-meshheading:18272581... | lld:pubmed |
| pubmed-article:18272581 | pubmed:meshHeading | pubmed-meshheading:18272581... | lld:pubmed |
