Linked Life Data

12890679

Source:http://linkedlifedata.com/resource/pubmed/id/12890679

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
40
pubmed:dateCreated
2003-9-29
pubmed:abstractText
The nuclear factor kappaB (NF-kappaB)/Rel family of transcription factors participates in a wide range of biological activities including inflammation, immunity, and apoptosis. NF-kappaB is kept inactive in the cytoplasm in unstimulated cells by virtue of the masking of its nuclear localization sequence by bound IkappaB protein. Cellular stimuli trigger the destruction of IkappaB proteins and the liberation of NF-kappaB to enter the nucleus and activate gene expression. A multisubunit IkappaB kinase complex (IKK) phosphorylates IkappaB proteins and mediates the activation of NF-kappaB by proinflammatory stimuli such as tumor necrosis factor alpha. Phosphorylation of IkappaB proteins triggers their polyubiquitination and their subsequent recognition and degradation by the proteasome. The IKK complex contains two catalytic subunits, IKKalpha and IKKbeta, and a noncatalytic subunit, NF-kappaB essential modifier/IKKgamma. IKK activation depends upon the phosphorylation of residues in the activation loop of IKKbeta and the subsequent activation of IKKbeta kinase activity. However, the events contributing to IKKbeta phosphorylation are not well understood. Here, we present evidence that the activation of IKKbeta depends on its ability to form homotypic interactions and to transautophosphorylate. We find that an intact leucine zipper in IKKbeta is necessary for homotypic interactions, kinase activation, and phosphorylation on its activation loop. Enforced oligomerization of an IKKbeta mutant defective in forming homotypic interactions restores kinase activation. Homotypic interactions allow IKKbeta molecules to transautophosphorylate one another on their activation loops. Finally, the oligomerization of IKKbeta is stimulated by tumor necrosis factor alpha in cultured cells. Our findings support a model whereby ligand-induced homotypic interactions between IKKbeta molecules result in IKKbeta phosphorylation and consequently IKK activation.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
38566-70
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12890679-Cell Line, pubmed-meshheading:12890679-Cell Nucleus, pubmed-meshheading:12890679-Dose-Response Relationship, Drug, pubmed-meshheading:12890679-Enzyme Activation, pubmed-meshheading:12890679-Gene Expression Regulation, pubmed-meshheading:12890679-Genetic Vectors, pubmed-meshheading:12890679-HeLa Cells, pubmed-meshheading:12890679-Humans, pubmed-meshheading:12890679-I-kappa B Kinase, pubmed-meshheading:12890679-Leucine, pubmed-meshheading:12890679-Ligands, pubmed-meshheading:12890679-Mutation, pubmed-meshheading:12890679-NF-kappa B, pubmed-meshheading:12890679-Phosphorylation, pubmed-meshheading:12890679-Plasmids, pubmed-meshheading:12890679-Precipitin Tests, pubmed-meshheading:12890679-Protein Binding, pubmed-meshheading:12890679-Protein-Serine-Threonine Kinases, pubmed-meshheading:12890679-Serine, pubmed-meshheading:12890679-Transfection, pubmed-meshheading:12890679-Tumor Necrosis Factor-alpha
pubmed:year
2003
pubmed:articleTitle
Roles for homotypic interactions and transautophosphorylation in IkappaB kinase beta IKKbeta) activation [corrected].
pubmed:affiliation
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. edtang@umich.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't