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Abstract:

The three related 160-kDa proteins, SRC-1, TIF-2 and RAC-3, were initially identified 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-κB. The aim of this work was to identify whether SRC-1 interferes with the TGF-β/Smad signaling pathway, and if so, to identify its underlying mechanisms of action. Using transient cell transfection experiments performed in human dermal fibroblasts with the Smad3/4-specific (SBE) 4-lux reporter construct, as well as the human PAI-1 promoter, we determined that SRC-1 enhances TGF-β-induced, Smad-mediated, transcription. Likewise, SRC-1 overexpression potentiated TGF-β-induced 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. © 2005 Nature Publishing Group All rights reserved.

Registro:

Documento: Artículo
Título:The steroid receptor co-activator-1 (SRC-1) potentiates TGF-β/Smad signaling: Role of p300/CBP
Autor:Dennler, S.; Pendaries, V.; Tacheau, C.; Costas, M.A.; Mauviel, A.; Verrecchia, F.
Filiación:INSERM U697, Institut de Recherche sur la Peau, Hôpital Saint-Louis, Paris, France
Deparmento de Cs. Biologicas, Fac. de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina
INSERM U697, Institut de Recherche sur la Peau, Hôpital Saint-Louis, 1, Avenue Claude Vellefaux, 75475 Paris Cedex 10, France
Palabras clave:p300; Smad; SRC-1 TGF-β; E1A protein; messenger RNA; oncoprotein; protein p300; recombinant transforming growth factor beta1; Smad protein; Smad3 protein; Smad4 protein; steroid receptor coactivator 1; virus protein; DNA binding protein; histone acetyltransferase; nuclear protein; Smad protein; steroid receptor coactivator 1; transactivator protein; transcription factor; transforming growth factor beta; Adenovirus; apoptosis; article; dermis; DNA binding; gel mobility shift assay; gene overexpression; genetic transcription; genetic transfection; human; human cell; nonhuman; Northern blotting; plasmid; priority journal; protein protein interaction; reporter gene; signal transduction; skin fibroblast; cell line; fibroblast; male; metabolism; newborn; physiology; skin; Adenoviridae; Mammalia; Cell Line; DNA-Binding Proteins; Fibroblasts; Genes, Reporter; Histone Acetyltransferases; Humans; Infant, Newborn; Male; Nuclear Proteins; Plasmids; Signal Transduction; Skin; Smad Proteins; Trans-Activators; Transcription Factors; Transcription, Genetic; Transfection; Transforming Growth Factor beta
Año:2005
Volumen:24
Número:11
Página de inicio:1936
Página de fin:1945
DOI: http://dx.doi.org/10.1038/sj.onc.1208343
Título revista:Oncogene
Título revista abreviado:Oncogene
ISSN:09509232
CODEN:ONCNE
CAS:Smad protein, 62395-38-4; Smad3 protein, 237417-78-6, 237417-96-8, 237418-00-7; Smad4 protein, 282562-18-9; histone acetyltransferase, 9054-51-7; DNA-Binding Proteins; Histone Acetyltransferases, EC 2.3.1.48; Nuclear Proteins; nuclear receptor coactivator 1, EC 2.3.1.48; Smad Proteins; Trans-Activators; Transcription Factors; Transforming Growth Factor beta
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_09509232_v24_n11_p1936_Dennler.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09509232_v24_n11_p1936_Dennler

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Citas:

---------- APA ----------
Dennler, S., Pendaries, V., Tacheau, C., Costas, M.A., Mauviel, A. & Verrecchia, F. (2005) . The steroid receptor co-activator-1 (SRC-1) potentiates TGF-β/Smad signaling: Role of p300/CBP. Oncogene, 24(11), 1936-1945.
http://dx.doi.org/10.1038/sj.onc.1208343
---------- CHICAGO ----------
Dennler, S., Pendaries, V., Tacheau, C., Costas, M.A., Mauviel, A., Verrecchia, F. "The steroid receptor co-activator-1 (SRC-1) potentiates TGF-β/Smad signaling: Role of p300/CBP" . Oncogene 24, no. 11 (2005) : 1936-1945.
http://dx.doi.org/10.1038/sj.onc.1208343
---------- MLA ----------
Dennler, S., Pendaries, V., Tacheau, C., Costas, M.A., Mauviel, A., Verrecchia, F. "The steroid receptor co-activator-1 (SRC-1) potentiates TGF-β/Smad signaling: Role of p300/CBP" . Oncogene, vol. 24, no. 11, 2005, pp. 1936-1945.
http://dx.doi.org/10.1038/sj.onc.1208343
---------- VANCOUVER ----------
Dennler, S., Pendaries, V., Tacheau, C., Costas, M.A., Mauviel, A., Verrecchia, F. The steroid receptor co-activator-1 (SRC-1) potentiates TGF-β/Smad signaling: Role of p300/CBP. Oncogene. 2005;24(11):1936-1945.
http://dx.doi.org/10.1038/sj.onc.1208343