Linked Life Data

16888014

Source:http://linkedlifedata.com/resource/pubmed/id/16888014

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2006-8-4
pubmed:abstractText
The NF-kappaB transcription factors are key regulators of immunomodulatory, cell cycle, and developmental gene regulation. NF-kappaB activity is mainly regulated through the phosphorylation of IkappaB by the IkappaB kinase (IKK) complex IKKalphabetagamma, leading to proteasome-mediated degradation of IkappaB, nuclear translocation of NF-kappaB dimers, DNA binding, and gene induction. Additionally, direct posttranslational modifications of NF-kappaB p65 and cRel subunits involving C-terminal phosphorylation has been demonstrated. The noncanonical IKK-related homologs, TNFR-associated factor family member-associated NF-kappaB activator (TANK)-binding kinase (TBK)1 and IKKepsilon, are also thought to play a role in NF-kappaB regulation, but their functions remain unclear. TBK1 and IKKepsilon were recently described as essential regulators of IFN gene activation through direct phosphorylation of the IFN regulatory factor-3 and -7 transcription factors. In the present study, we sought to determine whether IKKepsilon and TBK1 could modulate cRel activity via phosphorylation. TBK1 and IKKepsilon directly phosphorylate the C-terminal domain of cRel in vitro and in vivo and regulate nuclear accumulation of cRel, independently of the classical IkappaB/IKK pathway. IkappaBalpha degradation is not affected, but rather IKKepsilon-mediated phosphorylation of cRel leads to dissociation of the IkappaBalpha-cRel complex. These results illustrate a previously unrecognized aspect of cRel regulation, controlled by direct IKKepsilon/TBK1 phosphorylation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
177
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2527-35
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Nuclear accumulation of cRel following C-terminal phosphorylation by TBK1/IKK epsilon.
pubmed:affiliation
Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, 3755 chemin de la Cote Sainte Catherine, Montréal, Québec, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't