The steroid receptor co-activator-1 (SRC-1) potentiates TGF-β/Smad signaling: role of p300/CBP

Autores
Dennler, Sylviane; Pendaries, Valérie; Tacheau, Charlotte; Costas, Monica Alejandra; Mauviel, Alain; Verrecchia, Franck
Año de publicación
2005
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The three related 160-kDa proteins, SRC-1, TIF-2 and RAC-3, were initially identi•ed as factors interacting with nuclear receptors. They have also been reported to potentiate the activity of other transcription factors such as AP-1 or NF-jB. The aimof this work was to identify whether SRC-1 interferes with the TGF-b/Smad signaling pathway, and if so, to identify its underlying mechanisms of action. Using transient cell transfection experiments performed in human dermal •broblasts with the Smad3/4- speci•c (SBE)4-lux reporter construct, as well as the human PAI-1 promoter, we determined that SRC-1 enhances TGF-b-induced, Smad-mediated, transcription. Likewise, SRC-1 overexpression potentiated TGF-binduced upregulation of PAI-1 steady-state mRNA levels. Using a mammalian two-hybrid system, we demonstrated that SRC-1 interacts with the transcriptional co-activators p300/CBP, but not with Smad3. Overexpression of the adenovirus E1A oncoprotein, an inhibitor of CBP/ p300 activity, prevented the enhancing effect of SRC-1 on Smad3/4-mediated transcription, indicating that p300/ CBP may be required for SRC-1 effect. Such hypothesis was validated, as expression of a mutant form of SRC-1 lacking the CBP/p300-binding site failed to upregulate Smad3/4-dependent transcription, while full-length SRC- 1 potentiated p300 . Smad3 interactions. These results identify SRC-1 as a novel Smad3/4 transcriptional partner, facilitating the functional link between Smad3 and p300/CBP.
Fil: Dennler, Sylviane. Hôpital Saint-Louis; Francia. Inserm; Francia
Fil: Pendaries, Valérie. Hôpital Saint-Louis; Francia. Inserm; Francia
Fil: Tacheau, Charlotte. Inserm; Francia. Hôpital Saint-Louis; Francia
Fil: Costas, Monica Alejandra. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Mauviel, Alain. Hôpital Saint-Louis; Francia. Inserm; Francia
Fil: Verrecchia, Franck. Hôpital Saint-Louis; Francia. Inserm; Francia
Materia
p300
Smad
SRC-1 TGF-b
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/108439
Acceder
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network_name_str CONICET Digital (CONICET)
spelling The steroid receptor co-activator-1 (SRC-1) potentiates TGF-β/Smad signaling: role of p300/CBPDennler, SylvianePendaries, ValérieTacheau, CharlotteCostas, Monica AlejandraMauviel, AlainVerrecchia, Franckp300SmadSRC-1 TGF-bhttps://purl.org/becyt/ford/3.5https://purl.org/becyt/ford/3The three related 160-kDa proteins, SRC-1, TIF-2 and RAC-3, were initially identi•ed as factors interacting with nuclear receptors. They have also been reported to potentiate the activity of other transcription factors such as AP-1 or NF-jB. The aimof this work was to identify whether SRC-1 interferes with the TGF-b/Smad signaling pathway, and if so, to identify its underlying mechanisms of action. Using transient cell transfection experiments performed in human dermal •broblasts with the Smad3/4- speci•c (SBE)4-lux reporter construct, as well as the human PAI-1 promoter, we determined that SRC-1 enhances TGF-b-induced, Smad-mediated, transcription. Likewise, SRC-1 overexpression potentiated TGF-binduced upregulation of PAI-1 steady-state mRNA levels. Using a mammalian two-hybrid system, we demonstrated that SRC-1 interacts with the transcriptional co-activators p300/CBP, but not with Smad3. Overexpression of the adenovirus E1A oncoprotein, an inhibitor of CBP/ p300 activity, prevented the enhancing effect of SRC-1 on Smad3/4-mediated transcription, indicating that p300/ CBP may be required for SRC-1 effect. Such hypothesis was validated, as expression of a mutant form of SRC-1 lacking the CBP/p300-binding site failed to upregulate Smad3/4-dependent transcription, while full-length SRC- 1 potentiated p300 . Smad3 interactions. These results identify SRC-1 as a novel Smad3/4 transcriptional partner, facilitating the functional link between Smad3 and p300/CBP.Fil: Dennler, Sylviane. Hôpital Saint-Louis; Francia. Inserm; FranciaFil: Pendaries, Valérie. Hôpital Saint-Louis; Francia. Inserm; FranciaFil: Tacheau, Charlotte. Inserm; Francia. Hôpital Saint-Louis; FranciaFil: Costas, Monica Alejandra. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Mauviel, Alain. Hôpital Saint-Louis; Francia. Inserm; FranciaFil: Verrecchia, Franck. Hôpital Saint-Louis; Francia. Inserm; FranciaNature Publishing Group2005-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/108439Dennler, Sylviane; Pendaries, Valérie; Tacheau, Charlotte; Costas, Monica Alejandra; Mauviel, Alain; et al.; The steroid receptor co-activator-1 (SRC-1) potentiates TGF-β/Smad signaling: role of p300/CBP; Nature Publishing Group; Oncogene; 24; 11; 1-2005; 1936-19450950-9232CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/1208343info:eu-repo/semantics/altIdentifier/doi/10.1038/sj.onc.1208343info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:08:13Zoai:ri.conicet.gov.ar:11336/108439instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:08:13.553CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The steroid receptor co-activator-1 (SRC-1) potentiates TGF-β/Smad signaling: role of p300/CBP
title The steroid receptor co-activator-1 (SRC-1) potentiates TGF-β/Smad signaling: role of p300/CBP
spellingShingle The steroid receptor co-activator-1 (SRC-1) potentiates TGF-β/Smad signaling: role of p300/CBP
Dennler, Sylviane
p300
Smad
SRC-1 TGF-b
title_short The steroid receptor co-activator-1 (SRC-1) potentiates TGF-β/Smad signaling: role of p300/CBP
title_full The steroid receptor co-activator-1 (SRC-1) potentiates TGF-β/Smad signaling: role of p300/CBP
title_fullStr The steroid receptor co-activator-1 (SRC-1) potentiates TGF-β/Smad signaling: role of p300/CBP
title_full_unstemmed The steroid receptor co-activator-1 (SRC-1) potentiates TGF-β/Smad signaling: role of p300/CBP
title_sort The steroid receptor co-activator-1 (SRC-1) potentiates TGF-β/Smad signaling: role of p300/CBP
dc.creator.none.fl_str_mv Dennler, Sylviane
Pendaries, Valérie
Tacheau, Charlotte
Costas, Monica Alejandra
Mauviel, Alain
Verrecchia, Franck
author Dennler, Sylviane
author_facet Dennler, Sylviane
Pendaries, Valérie
Tacheau, Charlotte
Costas, Monica Alejandra
Mauviel, Alain
Verrecchia, Franck
author_role author
author2 Pendaries, Valérie
Tacheau, Charlotte
Costas, Monica Alejandra
Mauviel, Alain
Verrecchia, Franck
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv p300
Smad
SRC-1 TGF-b
topic p300
Smad
SRC-1 TGF-b
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.5
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The three related 160-kDa proteins, SRC-1, TIF-2 and RAC-3, were initially identi•ed as factors interacting with nuclear receptors. They have also been reported to potentiate the activity of other transcription factors such as AP-1 or NF-jB. The aimof this work was to identify whether SRC-1 interferes with the TGF-b/Smad signaling pathway, and if so, to identify its underlying mechanisms of action. Using transient cell transfection experiments performed in human dermal •broblasts with the Smad3/4- speci•c (SBE)4-lux reporter construct, as well as the human PAI-1 promoter, we determined that SRC-1 enhances TGF-b-induced, Smad-mediated, transcription. Likewise, SRC-1 overexpression potentiated TGF-binduced upregulation of PAI-1 steady-state mRNA levels. Using a mammalian two-hybrid system, we demonstrated that SRC-1 interacts with the transcriptional co-activators p300/CBP, but not with Smad3. Overexpression of the adenovirus E1A oncoprotein, an inhibitor of CBP/ p300 activity, prevented the enhancing effect of SRC-1 on Smad3/4-mediated transcription, indicating that p300/ CBP may be required for SRC-1 effect. Such hypothesis was validated, as expression of a mutant form of SRC-1 lacking the CBP/p300-binding site failed to upregulate Smad3/4-dependent transcription, while full-length SRC- 1 potentiated p300 . Smad3 interactions. These results identify SRC-1 as a novel Smad3/4 transcriptional partner, facilitating the functional link between Smad3 and p300/CBP.
Fil: Dennler, Sylviane. Hôpital Saint-Louis; Francia. Inserm; Francia
Fil: Pendaries, Valérie. Hôpital Saint-Louis; Francia. Inserm; Francia
Fil: Tacheau, Charlotte. Inserm; Francia. Hôpital Saint-Louis; Francia
Fil: Costas, Monica Alejandra. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Mauviel, Alain. Hôpital Saint-Louis; Francia. Inserm; Francia
Fil: Verrecchia, Franck. Hôpital Saint-Louis; Francia. Inserm; Francia
description The three related 160-kDa proteins, SRC-1, TIF-2 and RAC-3, were initially identi•ed as factors interacting with nuclear receptors. They have also been reported to potentiate the activity of other transcription factors such as AP-1 or NF-jB. The aimof this work was to identify whether SRC-1 interferes with the TGF-b/Smad signaling pathway, and if so, to identify its underlying mechanisms of action. Using transient cell transfection experiments performed in human dermal •broblasts with the Smad3/4- speci•c (SBE)4-lux reporter construct, as well as the human PAI-1 promoter, we determined that SRC-1 enhances TGF-b-induced, Smad-mediated, transcription. Likewise, SRC-1 overexpression potentiated TGF-binduced upregulation of PAI-1 steady-state mRNA levels. Using a mammalian two-hybrid system, we demonstrated that SRC-1 interacts with the transcriptional co-activators p300/CBP, but not with Smad3. Overexpression of the adenovirus E1A oncoprotein, an inhibitor of CBP/ p300 activity, prevented the enhancing effect of SRC-1 on Smad3/4-mediated transcription, indicating that p300/ CBP may be required for SRC-1 effect. Such hypothesis was validated, as expression of a mutant form of SRC-1 lacking the CBP/p300-binding site failed to upregulate Smad3/4-dependent transcription, while full-length SRC- 1 potentiated p300 . Smad3 interactions. These results identify SRC-1 as a novel Smad3/4 transcriptional partner, facilitating the functional link between Smad3 and p300/CBP.
publishDate 2005
dc.date.none.fl_str_mv 2005-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/108439
Dennler, Sylviane; Pendaries, Valérie; Tacheau, Charlotte; Costas, Monica Alejandra; Mauviel, Alain; et al.; The steroid receptor co-activator-1 (SRC-1) potentiates TGF-β/Smad signaling: role of p300/CBP; Nature Publishing Group; Oncogene; 24; 11; 1-2005; 1936-1945
0950-9232
CONICET Digital
CONICET
url http://hdl.handle.net/11336/108439
identifier_str_mv Dennler, Sylviane; Pendaries, Valérie; Tacheau, Charlotte; Costas, Monica Alejandra; Mauviel, Alain; et al.; The steroid receptor co-activator-1 (SRC-1) potentiates TGF-β/Smad signaling: role of p300/CBP; Nature Publishing Group; Oncogene; 24; 11; 1-2005; 1936-1945
0950-9232
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/1208343
info:eu-repo/semantics/altIdentifier/doi/10.1038/sj.onc.1208343
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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