Smad3-Smad4 and AP-1 complexes synergize in transcriptional activation of the c-Jun promoter by transforming growth factor beta.
Transcriptional regulation by transforming growth factor beta (TGF-beta) is a complex process which is likely to involve cross talk between different DNA responsive elements and transcription factors to achieve maximal promoter activation and specificity. Here, we describe a concurrent requirement for two discrete responsive elements in the regulation of the c-Jun promoter, one a binding site for a Smad3-Smad4 complex and the other an AP-1 binding site. The two elements are located 120 bp apart in the proximal c-Jun promoter, and each was able to independently bind its corresponding transcription factor complex. The effects of independently mutating each of these elements were nonadditive; disruption of either sequence resulted in complete or severe reductions in TGF-beta responsiveness. This simultaneous requirement for two distinct and independent DNA binding elements suggests that Smad and AP-1 complexes function synergistically to mediate TGF-beta-induced transcriptional activation of the c-Jun promoter.
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- Transforming Growth Factor beta
- Transcriptional Activation
- Transcription Factor AP-1
- Trans-Activators
- TATA Box
- Smad4 Protein
- Smad3 Protein
- Rabbits
- Proto-Oncogene Proteins c-jun
- Promoter Regions, Genetic
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transforming Growth Factor beta
- Transcriptional Activation
- Transcription Factor AP-1
- Trans-Activators
- TATA Box
- Smad4 Protein
- Smad3 Protein
- Rabbits
- Proto-Oncogene Proteins c-jun
- Promoter Regions, Genetic