Linked Life Data

10201927

Source:http://linkedlifedata.com/resource/pubmed/id/10201927

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1999-5-13
pubmed:abstractText
Transcription of the TNF gene is rapidly and transiently induced by LPS in cells of monocyte/macrophage lineage. Previous data suggested that multiple NF-kappaB/Rel binding sites play a role in the transcriptional response to LPS of the murine gene. However, the relevance of homologous sites in the human TNF gene remained a matter of controversy, partly because the high affinity NF-kappaB/Rel site located at -510 in the murine promoter is not conserved in humans. Here we used two sets of similarly designed human and mouse TNF promoter deletion constructs and overexpression of IkappaB in the murine macrophage cell line ANA-1 to show remarkable similarity in the pattern of the transcriptional response to LPS, further demonstrating the functional role of the distal promoter region located between -600 and -650. This region was characterized by mutagenesis of protein binding sites, including two relatively low affinity NF-kappaB/Rel sites, #2 and 2a. Mutation in each of the NF-kappaB sites resulted in 2- to 3-fold lower transcriptional activity in response to LPS. In contrast to LPS activation, the response to PMA was substantially lower in magnitude and required only the proximal promoter region. In summary, the functional topography of human and murine promoters when assayed in the same system has some marked similarities. Our observations support the notion that full LPS response of TNF gene requires both NF-kappaB and non-NF-kappaB nuclear proteins. Our data also suggest that the functional activity of a given kappaB site depends on the entire DNA sequence context in the promoter region.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
162
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4045-52
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Similarities and differences between human and murine TNF promoters in their response to lipopolysaccharide.
pubmed:affiliation
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow. kupras@imb.ac.ru
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't