Characterization of human FAST-1, a TGF beta and activin signal transducer

Mol Cell. 1998 Jul;2(1):121-7. doi: 10.1016/s1097-2765(00)80120-3.

Abstract

We have identified a human homolog of the Xenopus forkhead activin signal transducer-1 (xFAST-1). Although significantly different in sequence from its Xenopus counterpart, hFAST-1 shared with xFAST-1 the ability to bind to human Smad2 and activate an activin response element (ARE). The hFAST-1-dependent activation of ARE was completely dependent on endogenous Smad4 and stimulation by a TGF beta-like ligand. The hFAST-1 protein was shown to bind to a novel DNA motif, TGT (G/T) (T/G)ATT, an exact copy of which was present within the ARE. A single copy of this motif could activate a reporter in a TGF beta-dependent fashion but only when an adjacent Smad-binding element was present in the construct. These data suggest that responses to TGF beta family members may be mediated by a DNA-binding complex formed by hFAST-1, hSmad2, and hSmad4.

Publication types

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

MeSH terms

  • Activins
  • Amino Acid Sequence
  • Animals
  • Cloning, Molecular
  • Consensus Sequence
  • DNA / genetics
  • DNA, Neoplasm / genetics
  • DNA-Binding Proteins / physiology*
  • Forkhead Transcription Factors
  • Gene Expression Regulation / physiology*
  • Humans
  • Inhibins / physiology*
  • Macromolecular Substances
  • Mice
  • Mice, Nude
  • Molecular Sequence Data
  • Nerve Growth Factors
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction / physiology*
  • Smad Proteins
  • Smad2 Protein
  • Smad4 Protein
  • Trans-Activators / physiology
  • Transcription Factors / physiology*
  • Transforming Growth Factor beta / physiology*
  • Xenopus Proteins*

Substances

  • DNA, Neoplasm
  • DNA-Binding Proteins
  • FOXH1 protein, human
  • Forkhead Transcription Factors
  • Foxh1 protein, mouse
  • Macromolecular Substances
  • Nerve Growth Factors
  • SMAD2 protein, human
  • SMAD4 protein, human
  • Smad Proteins
  • Smad2 Protein
  • Smad2 protein, mouse
  • Smad4 Protein
  • Smad4 protein, mouse
  • Trans-Activators
  • Transcription Factors
  • Transforming Growth Factor beta
  • Xenopus Proteins
  • smad4.1 protein, Xenopus
  • smad4.2 protein, Xenopus
  • Activins
  • Inhibins
  • DNA

Associated data

  • GENBANK/AF076292