Characterization of human FAST-1, a TGF beta and activin signal transducer.
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.
Howard Hughes Medical Institute, Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA.
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S
Zhou
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Zawel
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Lengauer
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KW
Kinzler
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B
Vogelstein
D028341:Activins; D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D016384:Consensus Sequence; D004247:DNA / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000502:physiology*; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007265:Inhibins / Q000502:physiology*; D046911:Macromolecular Substances; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins; D051899:Smad2 Protein; D051901:Smad4 Protein; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*; D029867:Xenopus Proteins
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C510350:FOXH1 protein, human; D051858:Forkhead Transcription Factors; C491117:Foxh1 protein, mouse; D046911:Macromolecular Substances; D009414:Nerve Growth Factors; C497782:SMAD2 protein, human; C497796:SMAD4 protein, human; D051785:Smad Proteins; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; C490808:smad4.1 protein, Xenopus; C117263:smad4.2 protein, Xenopus; D028341:Activins; D007265:Inhibins; D004247:DNA