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Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription

Y Zhang1, X H Feng, R Derynck

  • 1Department of Growth and Development, Program in Cell Biology, University of California at San Francisco, 94143-0640, USA.

Nature
|September 11, 1998
PubMed

Insights

Smad3 and Smad4 proteins activate gene transcription through AP1-binding sites, interacting with both Smad and AP-1 factors. This reveals a convergence of Smad and MAPK/JNK signaling pathways.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Gene Regulation

Background:

  • Smad proteins mediate transforming growth factor-beta (TGF-beta) signaling.
  • TGF-beta signaling regulates gene transcription via Smad complexes.
  • AP-1 transcription factors (c-Jun, c-Fos) bind to TPA-responsive elements (TREs).

Purpose of the Study:

  • To investigate the interaction of Smad proteins with TREs.
  • To determine if Smad proteins can activate transcription independently of AP-1 factors.
  • To elucidate the mechanism of TGF-beta-induced transcription involving Smad and AP-1 factors.

Main Methods:

  • Direct interaction assays between Smad3 and TREs.
  • Analysis of TGF-beta-inducible transcription activation.
  • Investigation of protein-protein interactions (Smad3, Smad4, c-Jun, c-Fos).

Main Results:

  • Smad3 directly interacts with TREs.
  • Smad3 and Smad4 activate TGF-beta-inducible transcription from TREs without c-Jun/c-Fos.
  • Smad3 and Smad4 cooperate with c-Jun/c-Fos for TGF-beta-induced transcription via novel interactions.

Conclusions:

  • Smad signaling and MAPK/JNK signaling converge at AP1-binding promoter sites.
  • Functional and physical interactions between Smad3-Smad4 and c-Jun-c-Fos mediate TGF-beta transcriptional activation.
  • This study reveals a novel mechanism for TGF-beta-regulated gene expression.

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