Abstract
Wnt signaling plays an important role in embryonic development and tumorigenesis. These biological effects are exerted by activation of the beta-catenin/TCF transcription complex and consequent regulation of a set of downstream genes. TCF-binding elements have been found in the promoter regions of many TCF target genes and characterized by a highly conserved consensus sequence. Utilizing this consensus sequence, we performed an in silico screening for new TCF target genes. Through computational screening and subsequent experimental analysis, we identified a novel TCF target gene, DKK1, which has been shown to be a potent inhibitor of Wnt signaling. Our finding suggests the existence of a novel feedback loop in Wnt signaling.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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Binding Sites
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Computational Biology
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Cytoskeletal Proteins / metabolism*
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Drosophila Proteins / metabolism
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Feedback, Physiological / physiology
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Gene Expression Regulation / physiology
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Humans
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Intercellular Signaling Peptides and Proteins
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Mice
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Molecular Sequence Data
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Promoter Regions, Genetic
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Proteins / metabolism*
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Proto-Oncogene Proteins / metabolism*
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Repressor Proteins / metabolism
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Trans-Activators / metabolism*
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Transcription Factors / metabolism*
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Wnt Proteins
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beta Catenin
Substances
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CTNNB1 protein, human
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CTNNB1 protein, mouse
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Cytoskeletal Proteins
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DKK1 protein, human
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Dkk1 protein, mouse
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Drosophila Proteins
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Intercellular Signaling Peptides and Proteins
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Proteins
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Proto-Oncogene Proteins
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Repressor Proteins
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Trans-Activators
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Transcription Factors
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Wnt Proteins
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beta Catenin
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pan protein, Drosophila