Linked Life Data

11402315

Source:http://linkedlifedata.com/resource/pubmed/id/11402315

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2001-6-12
pubmed:abstractText
Smad proteins transduce signals from TGF-beta receptors and regulate transcription of target genes. Among the latter are c-jun and junB, which encode members of the AP-1 family of transcription factors. In this study, we have investigated the functional interactions of the Smad and AP-1 transcription factors in the context of Smad-specific gene transactivation in both fibroblasts and keratinocytes. We demonstrate that overexpression of either junB or c-jun prevents TGF-beta- or Smad3-induced transactivation of the Smad-specific promoter construct (SBE)(4)-Lux. Inversely, Smad-driven promoter transactivation by TGF-beta/Smad is significantly enhanced when c-jun expression is abolished in HaCaT keratinocytes, and when junB expression is prevented in fibroblasts, consistent with the cell-type specific induction of jun members by TGF-beta. We also demonstrate that Smad-specific gene transactivation in junB(-/-) mouse embryonic fibroblasts is significantly higher than in embryonic fibroblasts from the control parental mouse line, and that this difference is abolished by rescuing junB expression in junB(-/-) cells. Finally, we have determined that off-DNA interactions between Smad3 and both c-Jun and JunB result in the reduction of Smad3/DNA interactions. From these results, we provide a model in which jun expression in response to the initial Smad cascade represents a negative feed-back mechanism counteracting Smad-driven gene transactivation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2205-11
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Induction of the AP-1 members c-Jun and JunB by TGF-beta/Smad suppresses early Smad-driven gene activation.
pubmed:affiliation
INSERM U532, Hôpital Saint-Louis, F-75010 Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't