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

摘要: 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 such AP-1 or NF-kappaB. aim this work was identify whether SRC-1 interferes TGF-beta/Smad signaling pathway, if so, its underlying mechanisms action. Using transient cell transfection experiments performed in human dermal fibroblasts Smad3/4-specific (SBE)4-lux reporter construct, well PAI-1 promoter, we determined that enhances TGF-beta-induced, Smad-mediated, transcription. Likewise, overexpression potentiated TGF-beta-induced upregulation steady-state mRNA levels. a mammalian two-hybrid system, demonstrated interacts transcriptional co-activators p300/CBP, but not Smad3. Overexpression adenovirus E1A oncoprotein, an inhibitor CBP/p300 activity, prevented enhancing effect on Smad3/4-mediated transcription, indicating p300/CBP may be required for effect. Such hypothesis validated, expression mutant form lacking CBP/p300-binding site failed upregulate Smad3/4-dependent while full-length p300.Smad3 interactions. These results novel Smad3/4 partner, facilitating functional link between Smad3 p300/CBP.