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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
|
pubmed:dateCreated |
1994-4-1
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pubmed:abstractText |
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.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
Feb
|
pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
25
|
pubmed:volume |
269
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pubmed:geneSymbol |
WT1
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
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pubmed:pagination |
6198-206
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:8119964-Base Sequence,
pubmed-meshheading:8119964-Binding Sites,
pubmed-meshheading:8119964-Cells, Cultured,
pubmed-meshheading:8119964-DNA,
pubmed-meshheading:8119964-Down-Regulation,
pubmed-meshheading:8119964-Gene Expression Regulation,
pubmed-meshheading:8119964-Genes, Wilms Tumor,
pubmed-meshheading:8119964-Humans,
pubmed-meshheading:8119964-Molecular Sequence Data,
pubmed-meshheading:8119964-Nephrons,
pubmed-meshheading:8119964-Promoter Regions, Genetic
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pubmed:year |
1994
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pubmed:articleTitle |
The Wilms' tumor suppressor gene WT1 is negatively autoregulated.
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pubmed:affiliation |
Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215.
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|