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PMID:8119964

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Citation

Rupprecht, HD, Drummond, IA, Madden, SL, Rauscher, FJ 3rd and Sukhatme, VP (1994) The Wilms' tumor suppressor gene WT1 is negatively autoregulated. J. Biol. Chem. 269:6198-206

Abstract

The Wilms' tumor suppressor gene WT1 encodes a zinc-finger DNA-binding protein that functions as a transcriptional repressor. WT1 is expressed in a dramatic spatial and temporal pattern during kidney development and is thought to be critical during mesenchymal-epithelial conversion. The WT1 protein bound multiple sites in the WT1 promoter and functioned as a powerful transcriptional repressor of its gene in vivo (> 50-fold). The WT1 protein carrying an NH2-terminal 17-amino acid insertion and a 3-amino acid insertion (KTS) between zinc fingers 3 and 4, arising from the most abundant of four alternatively spliced transcripts, was the most powerful repressor. Of importance, a subset of WT1-binding sites differs from the Egr-1 consensus sequence, which has been shown to bind one splice variant of the WT1 protein (WT1(-KTS)). We characterized two of these sites and show that they bind both -KTS and +KTS forms of the WT1 zinc-finger protein and can confer repression on a heterologous promoter construct. Our data demonstrate that WT1, in addition to its known effects on insulin-like growth factor II, platelet-derived growth factor A, and Pax-2 transcription, is a powerful repressor of its own gene. These observations emphasize its critical role as a transcriptional regulatory protein during normal kidney development.

Links

PubMed

Keywords

Base Sequence; Binding Sites; Cells, Cultured; DNA/metabolism; Down-Regulation; Gene Expression Regulation; Genes, Wilms Tumor; Humans; Molecular Sequence Data; Nephrons/metabolism; Promoter Regions, Genetic

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:WT1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P19544

F

Seeded From UniProt

complete

HUMAN:WT1

enables

GO:0070742: C2H2 zinc finger domain binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P19544

F

Seeded From UniProt

complete

HUMAN:WT1

enables

GO:0043565: sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:WT1

involved_in

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:WT1

enables

GO:0043565: sequence-specific DNA binding

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:P19544

F

Seeded From UniProt

complete

MOUSE:WT1

involved_in

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:P19544

P

Seeded From UniProt

complete

MOUSE:WT1

enables

GO:0070742: C2H2 zinc finger domain binding

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:P19544

F

Seeded From UniProt

complete


See also

References

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