Smad proteins have recently been identified as mediators of transcriptional activation by members of the transforming growth factor-β superfamily. To determine if Smads might also be involved in inducing gene transcription in response to other agonists, expression vectors for dominant-negative Smad proteins were constructed. These plasmids were transiently cotransfected with luciferase reporter genes and the effects of various agonists on reporter gene activity evaluated in NIH 3T3 cells. Dominant-negative Smad3, but not other dominant-negative Smads, reduced stimulation of the plasminogen activator inhibitor-1 (PAI-1) and other gene promoters by phorbol ester, cAMP, and platelet-derived growth factor. Activation of the PAI-1 promoter by TGF-β or prostaglandin F2α, and transactivation by c-Jun or JunB were not inhibited by dominant-negative Smads, supporting the specificity of this mutant. These results suggest that Smad3, like CREB-binding protein (CBP), may participate in transcriptional activation by multiple agonists.
|Number of pages||5|
|Journal||Biochemical and biophysical research communications|
|Publication status||Published - márc. 17 1997|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology