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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Activins
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Amino Acid Sequence
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Animals
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Cloning, Molecular
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Consensus Sequence
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DNA / genetics
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DNA, Neoplasm / genetics
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DNA-Binding Proteins / physiology*
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Forkhead Transcription Factors
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Gene Expression Regulation / physiology*
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Humans
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Inhibins / physiology*
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Macromolecular Substances
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Mice
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Mice, Nude
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Molecular Sequence Data
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Nerve Growth Factors
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Sequence Alignment
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Sequence Homology, Amino Acid
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Signal Transduction / physiology*
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Smad Proteins
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Smad2 Protein
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Smad4 Protein
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Trans-Activators / physiology
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Transcription Factors / physiology*
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Transforming Growth Factor beta / physiology*
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Xenopus Proteins*
Substances
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DNA, Neoplasm
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DNA-Binding Proteins
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FOXH1 protein, human
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Forkhead Transcription Factors
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Foxh1 protein, mouse
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Macromolecular Substances
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Nerve Growth Factors
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SMAD2 protein, human
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SMAD4 protein, human
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Smad Proteins
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Smad2 Protein
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Smad2 protein, mouse
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Smad4 Protein
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Smad4 protein, mouse
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Trans-Activators
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Transcription Factors
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Transforming Growth Factor beta
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Xenopus Proteins
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smad4.1 protein, Xenopus
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smad4.2 protein, Xenopus
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Activins
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Inhibins
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DNA