Binding of the Wilms' tumor locus zinc finger protein to the EGR-1 consensus sequence.
The Wilms' tumor locus (WTL) at 11p13 contains a gene that encodes a zinc finger-containing protein that has characteristics of a DNA-binding protein. However, binding of this protein to DNA in a sequence-specific manner has not been demonstrated. A synthetic gene was constructed that contained the zinc finger region, and the protein was expressed in Escherichia coli. The recombinant protein was used to identify a specific DNA binding site from a pool of degenerate oligonucleotides. The binding sites obtained were similar to the sequence recognized by the early growth response-1 (EGR-1) gene product, a zinc finger-containing protein that is induced by mitogenic stimuli. A mutation in the zinc finger region of the protein originally identified in a Wilms' tumor patient abolished its DNA-binding activity. These results suggest that the WTL protein may act at the DNA binding site of a growth factor-inducible gene and that loss of DNA-binding activity contributes to the tumorigenic process.
Rauscher
F J
FJ
Wistar Institute, Philadelphia, PA 19104.
Morris
J F
JF
Tournay
O E
OE
Cook
D M
DM
Curran
T
T
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D002880:Chromosomes, Human, Pair 11; D016384:Consensus Sequence; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051766:Early Growth Response Protein 1; D004926:Escherichia coli / Q000235:genetics; D016162:Genes, Wilms Tumor; D006801:Humans; D017874:Immediate-Early Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D009841:Oligonucleotides / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000378:metabolism; D015183:Restriction Mapping; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers / Q000235:genetics
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D009841:Oligonucleotides; D011994:Recombinant Proteins; D014157:Transcription Factors; D004247:DNA