Identification of a critical Sp1 site within the endoglin promoter and its involvement in the transforming growth factor-beta stimulation

10 p.-6 fig.

Detalles Bibliográficos
Autores: Botella, Luisa María, Sánchez-Elsner, Tilman, Rius, Carlos, Corbí, Angel L., Bernabéu, Carmelo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2001
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/168007
Acceso en línea:http://hdl.handle.net/10261/168007
Access Level:acceso abierto
Palabra clave:Hereditary hemorrhagic telangiectasia
Transcription factor sp1
Smad-binding-element
tgf-beta
dna-binding
Endothelial-cells
Functional interactions
Expression analysis
Cellular responses
Heart development
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spelling Identification of a critical Sp1 site within the endoglin promoter and its involvement in the transforming growth factor-beta stimulationBotella, Luisa MaríaSánchez-Elsner, TilmanRius, CarlosCorbí, Angel L.Bernabéu, CarmeloHereditary hemorrhagic telangiectasiaTranscription factor sp1Smad-binding-elementtgf-betadna-bindingEndothelial-cellsFunctional interactionsExpression analysisCellular responsesHeart development10 p.-6 fig.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.This work was supported in part by Ministerio de Ciencia y Tecnologı́a Grants SAF2000-0132 and SAF98/0068 and by the Comunidad Autónoma de Madrid.Peer reviewedAmerican Society for Biochemistry and Molecular BiologyMinisterio de Ciencia y Tecnología (España)Comunidad de MadridBotella, Luisa María [0000-0002-6310-2245]Sánchez-Elsner, Tilman [0000-0003-1915-2410]Corbí, Angel L.[0000-0003-1980-5733]Bernabéu, Carmelo [0000-0002-1563-6162]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201820182001info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/168007reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1074/jbc.M011611200Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1680072026-05-22T06:33:51Z
dc.title.none.fl_str_mv Identification of a critical Sp1 site within the endoglin promoter and its involvement in the transforming growth factor-beta stimulation
title Identification of a critical Sp1 site within the endoglin promoter and its involvement in the transforming growth factor-beta stimulation
spellingShingle Identification of a critical Sp1 site within the endoglin promoter and its involvement in the transforming growth factor-beta stimulation
Botella, Luisa María
Hereditary hemorrhagic telangiectasia
Transcription factor sp1
Smad-binding-element
tgf-beta
dna-binding
Endothelial-cells
Functional interactions
Expression analysis
Cellular responses
Heart development
title_short Identification of a critical Sp1 site within the endoglin promoter and its involvement in the transforming growth factor-beta stimulation
title_full Identification of a critical Sp1 site within the endoglin promoter and its involvement in the transforming growth factor-beta stimulation
title_fullStr Identification of a critical Sp1 site within the endoglin promoter and its involvement in the transforming growth factor-beta stimulation
title_full_unstemmed Identification of a critical Sp1 site within the endoglin promoter and its involvement in the transforming growth factor-beta stimulation
title_sort Identification of a critical Sp1 site within the endoglin promoter and its involvement in the transforming growth factor-beta stimulation
dc.creator.none.fl_str_mv Botella, Luisa María
Sánchez-Elsner, Tilman
Rius, Carlos
Corbí, Angel L.
Bernabéu, Carmelo
author Botella, Luisa María
author_facet Botella, Luisa María
Sánchez-Elsner, Tilman
Rius, Carlos
Corbí, Angel L.
Bernabéu, Carmelo
author_role author
author2 Sánchez-Elsner, Tilman
Rius, Carlos
Corbí, Angel L.
Bernabéu, Carmelo
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia y Tecnología (España)
Comunidad de Madrid
Botella, Luisa María [0000-0002-6310-2245]
Sánchez-Elsner, Tilman [0000-0003-1915-2410]
Corbí, Angel L.[0000-0003-1980-5733]
Bernabéu, Carmelo [0000-0002-1563-6162]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Hereditary hemorrhagic telangiectasia
Transcription factor sp1
Smad-binding-element
tgf-beta
dna-binding
Endothelial-cells
Functional interactions
Expression analysis
Cellular responses
Heart development
topic Hereditary hemorrhagic telangiectasia
Transcription factor sp1
Smad-binding-element
tgf-beta
dna-binding
Endothelial-cells
Functional interactions
Expression analysis
Cellular responses
Heart development
description 10 p.-6 fig.
publishDate 2001
dc.date.none.fl_str_mv 2001
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/168007
url http://hdl.handle.net/10261/168007
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1074/jbc.M011611200
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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