Human Smad3 and Smad4 are sequence-specific transcription activators

Mol Cell. 1998 Mar;1(4):611-7. doi: 10.1016/s1097-2765(00)80061-1.


Mounting evidence indicates that Smad proteins are required for TGF beta signaling, but the way(s) in which Smad proteins propagate this signal is unclear. We found that two human Smad proteins (Smad3 and Smad4) could specifically recognize an identical 8 bp palindromic sequences (GTCTAGAC). Tandem repeats of this palindrome conferred striking TGF beta responsiveness to a minimal promoter. This responsiveness was abrogated by targeted deletion of the cellular Smad4 gene. These results define a novel biochemical property of Smad proteins that is likely to play a direct role in the biologic responses to TGF beta and related ligands.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Consensus Sequence
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology
  • Genes, Tumor Suppressor / genetics
  • Humans
  • Protein Binding / physiology
  • Protein Structure, Tertiary
  • Signal Transduction / genetics
  • Smad3 Protein
  • Smad4 Protein
  • Trans-Activators / chemistry
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • Transcriptional Activation / genetics*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism


  • DNA-Binding Proteins
  • SMAD3 protein, human
  • SMAD4 protein, human
  • Smad3 Protein
  • Smad4 Protein
  • Trans-Activators
  • Transforming Growth Factor beta