Document Detail

Smad3-Smad4 and AP-1 complexes synergize in transcriptional activation of the c-Jun promoter by transforming growth factor beta.
MedLine Citation:
PMID:  10022869     Owner:  NLM     Status:  MEDLINE    
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.
C Wong; E M Rougier-Chapman; J P Frederick; M B Datto; N T Liberati; J M Li; X F Wang
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  19     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-03-25     Completed Date:  1999-03-25     Revised Date:  2013-04-17    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1821-30     Citation Subset:  IM    
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27708, USA.
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MeSH Terms
Amino Acid Sequence
Base Sequence
Binding Sites
Cell Line
Cells, Cultured
DNA-Binding Proteins / metabolism*
Gene Expression Regulation
Molecular Sequence Data
Promoter Regions, Genetic*
Proto-Oncogene Proteins c-jun / genetics*
Smad3 Protein
Smad4 Protein
Trans-Activators / metabolism*
Transcription Factor AP-1 / metabolism*
Transcriptional Activation*
Transforming Growth Factor beta / metabolism*
Grant Support
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Proto-Oncogene Proteins c-jun; 0/SMAD3 protein, human; 0/SMAD4 protein, human; 0/Smad3 Protein; 0/Smad3 protein, mouse; 0/Smad4 Protein; 0/Smad4 protein, mouse; 0/Trans-Activators; 0/Transcription Factor AP-1; 0/Transforming Growth Factor beta

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