Linked Life Data

11432852

Source:http://linkedlifedata.com/resource/pubmed/id/11432852

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
37
pubmed:dateCreated
2001-9-10
pubmed:abstractText
Endoglin, a component of the transforming growth factor-beta (TGF-beta) receptor complex expressed on endothelial cells, is involved in cardiovascular morphogenesis and vascular remodeling, as exemplified by the fact that the endoglin gene is the target for the autosomal dominant disorder known as hereditary hemorrhagic telangiectasia type 1. Since haploinsufficiency is the underlying mechanism for hereditary hemorrhagic telangiectasia type 1, understanding the regulation of endoglin gene expression appears to be a crucial step to correct the disease. In this study we have identified an Sp1 site at -37 as a critical element for the basal transcription of the endoglin TATA-less promoter. Since endoglin promoter activity is stimulated by TGF-beta and this stimulation is located at the Sp1-containing proximal region, we have investigated the possible involvement of Sp1 in the TGF-beta-mediated induction. Mutation of the Sp1-binding sequence, or addition of the Sp1 inhibitor WP631, abolished both the basal transcription activity and the TGF-beta responsiveness of the endoglin promoter. Binding of Sp1 and Smad3 to the proximal promoter region -50/-29 was evidenced by electrophoretic mobility shift assays and DNA affinity precipitation studies. Furthermore, synergistic cooperation on the promoter activity between Sp1 and TGF-beta or Smad3 could be demonstrated by co-transfection experiments of reporter promoter constructs. The molecular mechanism underlying this cooperation appears to involve a direct physical interaction between Sp1 and Smad3/Smad4.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD, http://linkedlifedata.com/resource/pubmed/chemical/DNA, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/ENG protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface, http://linkedlifedata.com/resource/pubmed/chemical/SMAD3 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/SMAD4 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Smad3 Protein, http://linkedlifedata.com/resource/pubmed/chemical/Smad4 Protein, http://linkedlifedata.com/resource/pubmed/chemical/Sp1 Transcription Factor, http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta, http://linkedlifedata.com/resource/pubmed/chemical/Vascular Cell Adhesion Molecule-1
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
34486-94
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Identification of a critical Sp1 site within the endoglin promoter and its involvement in the transforming growth factor-beta stimulation.
pubmed:affiliation
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Cientificas, Velázquez 144, 28006 Madrid, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't