Tags

Type your tag names separated by a space and hit enter

The steroid receptor co-activator-1 (SRC-1) potentiates TGF-beta/Smad signaling: role of p300/CBP.
Oncogene. 2005 Mar 10; 24(11):1936-45.O

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-kappaB. The aim of this work was to identify whether SRC-1 interferes with the TGF-beta/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-beta-induced, Smad-mediated, transcription. Likewise, SRC-1 overexpression potentiated TGF-beta-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.

Authors+Show Affiliations

INSERM U697, Institut de recherche sur la peau, Hôpital Saint-Louis, Paris, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15688032

Citation

Dennler, Sylviane, et al. "The Steroid Receptor Co-activator-1 (SRC-1) Potentiates TGF-beta/Smad Signaling: Role of P300/CBP." Oncogene, vol. 24, no. 11, 2005, pp. 1936-45.
Dennler S, Pendaries V, Tacheau C, et al. The steroid receptor co-activator-1 (SRC-1) potentiates TGF-beta/Smad signaling: role of p300/CBP. Oncogene. 2005;24(11):1936-45.
Dennler, S., Pendaries, V., Tacheau, C., Costas, M. A., Mauviel, A., & Verrecchia, F. (2005). The steroid receptor co-activator-1 (SRC-1) potentiates TGF-beta/Smad signaling: role of p300/CBP. Oncogene, 24(11), 1936-45.
Dennler S, et al. The Steroid Receptor Co-activator-1 (SRC-1) Potentiates TGF-beta/Smad Signaling: Role of P300/CBP. Oncogene. 2005 Mar 10;24(11):1936-45. PubMed PMID: 15688032.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The steroid receptor co-activator-1 (SRC-1) potentiates TGF-beta/Smad signaling: role of p300/CBP. AU - Dennler,Sylviane, AU - Pendaries,Valérie, AU - Tacheau,Charlotte, AU - Costas,Monica A, AU - Mauviel,Alain, AU - Verrecchia,Franck, PY - 2005/2/3/pubmed PY - 2005/4/15/medline PY - 2005/2/3/entrez SP - 1936 EP - 45 JF - Oncogene JO - Oncogene VL - 24 IS - 11 N2 - 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-kappaB. The aim of this work was to identify whether SRC-1 interferes with the TGF-beta/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-beta-induced, Smad-mediated, transcription. Likewise, SRC-1 overexpression potentiated TGF-beta-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. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/15688032/The_steroid_receptor_co_activator_1__SRC_1__potentiates_TGF_beta/Smad_signaling:_role_of_p300/CBP_ L2 - https://doi.org/10.1038/sj.onc.1208343 DB - PRIME DP - Unbound Medicine ER -