Smad3-Smad4 and AP-1 complexes synergize in transcriptional activation of the c-Jun promoter by transforming growth factor beta.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Wong, C; Rougier-Chapman, EM; Frederick, JP; Datto, MB; Liberati, NT; Li, JM; Wang, XF

Published Date

  • March 1999

Published In

Volume / Issue

  • 19 / 3

Start / End Page

  • 1821 - 1830

PubMed ID

  • 10022869

International Standard Serial Number (ISSN)

  • 0270-7306

Language

  • eng

Conference Location

  • United States