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Molecular and Cellular Biology, March 1999, p. 1821-1830, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Smad3-Smad4 and AP-1 Complexes Synergize in Transcriptional Activation of the c-Jun Promoter by Transforming Growth Factor beta

Carolyn Wong,1 Elissa M. Rougier-Chapman,1 Joshua P. Frederick,1 Michael B. Datto,1 Nicole T. Liberati,1 Jian-Ming Li,2 and Xiao-Fan Wang1,*

Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27708,1 and Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 208922

Received 25 August 1998/Returned for modification 6 October 1998/Accepted 2 November 1998

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.

* Corresponding author. Mailing address: Department of Pharmacology and Cancer Biology, Box 3813, Duke University Medical Center, Durham, NC 27708. Phone: (919) 681-4860. Fax: (919) 681-7152. E-mail: wang{at}galactose.mc.duke.edu.

Molecular and Cellular Biology, March 1999, p. 1821-1830, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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