Linked Life Data

10987817

Source:http://linkedlifedata.com/resource/pubmed/id/10987817

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2000-10-5
pubmed:abstractText
Signal transduction pathways that mediate neuronal commitment to apoptosis involve the nuclear factor kappaB (NF-kappaB) transcription factor. Bcl-X(L) is a potent regulator of apoptosis in the CNS and is highly expressed in the developing and adult brain. We identified three putative NF-kappaB DNA binding sequences clustered upstream of the brain-specific transcription start site in the upstream promoter region. Recombinant p50/p50 and NF-kappaB proteins from nuclear extracts bound to these sites as determined by electrophoretic mobility shift assay and biotin-oligonucleotide/streptavidin affinity assays. NF-kappaB overexpression, coupled with bcl-x promoter/reporter assays using a series of murine bcl-x promoter and deletion mutants, has identified the downstream 1.1 kb of the bcl-x promoter as necessary for basal promoter activity and induction by NF-kappaB. The mutagenic removal of NF-kappaB binding sites individually or in combination revealed altered response patterns to p49/p65 and p50/p65 overexpression. These results support the hypothesis that NF-kappaB can act to enhance Bcl-X(L) expression via highly selective interactions, where NF-kappaB binding and bcl-x promoter activation are dependent on both DNA binding site sequence and NF-kappaB subunit composition. Our data suggest that molecular events associated with NF-kappaB promote regulation of neuronal apoptosis in the developing or injured CNS.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
75
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1377-89
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10987817-5' Untranslated Regions, pubmed-meshheading:10987817-Animals, pubmed-meshheading:10987817-Apoptosis, pubmed-meshheading:10987817-Binding, Competitive, pubmed-meshheading:10987817-Binding Sites, pubmed-meshheading:10987817-DNA, pubmed-meshheading:10987817-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:10987817-Gene Expression Regulation, pubmed-meshheading:10987817-Genes, Reporter, pubmed-meshheading:10987817-Humans, pubmed-meshheading:10987817-Mice, pubmed-meshheading:10987817-NF-kappa B, pubmed-meshheading:10987817-NF-kappa B p50 Subunit, pubmed-meshheading:10987817-PC12 Cells, pubmed-meshheading:10987817-Promoter Regions, Genetic, pubmed-meshheading:10987817-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:10987817-Rats, pubmed-meshheading:10987817-Recombinant Proteins, pubmed-meshheading:10987817-Transcription Factor RelA, pubmed-meshheading:10987817-Transcriptional Activation, pubmed-meshheading:10987817-Transfection, pubmed-meshheading:10987817-bcl-X Protein
pubmed:year
2000
pubmed:articleTitle
Identification and characterization of nuclear factor kappaB binding sites in the murine bcl-x promoter.
pubmed:affiliation
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, Texas 77555-0652, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't