Abstract
Inappropriate activation of downstream target genes by the oncoprotein beta-catenin is implicated in development of numerous human cancers. beta-catenin and its fruitfly counterpart Armadillo act as a coactivator in the canonical Wnt/Wingless pathway by binding to Tcf/Lef transcription factors. Here we report a conserved nuclear protein, named Chibby, which was identified in a screen for proteins that directly interact with the C-terminal region of beta-catenin. In mammalian cultured cells we demonstrate that Chibby inhibits beta-catenin-mediated transcriptional activation by competing with Lef-1 to bind to beta-catenin. Inhibition of Drosophila Chibby by RNA interference results in segment polarity defects that mimick a wingless gain-of-function phenotype, and overexpression of the wingless target genes engrailed and Ultrabithorax. In addition, epistasis experiments indicate that chibby acts downstream of wingless and upstream of armadillo.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Armadillo Domain Proteins
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Binding Sites
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COS Cells
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Line
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Conserved Sequence
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Cytoskeletal Proteins / antagonists & inhibitors
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Cytoskeletal Proteins / chemistry
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Cytoskeletal Proteins / metabolism*
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Drosophila Proteins / chemistry
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Drosophila melanogaster / genetics
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Epistasis, Genetic
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Homeodomain Proteins / genetics
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Humans
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Lymphoid Enhancer-Binding Factor 1
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Molecular Sequence Data
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Nuclear Proteins / chemistry
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Phenotype
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Protein Binding
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Proto-Oncogene Proteins / antagonists & inhibitors*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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RNA Interference
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Signal Transduction*
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Trans-Activators / antagonists & inhibitors
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Trans-Activators / chemistry
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcriptional Activation
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Wnt Proteins
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Wnt1 Protein
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Zebrafish Proteins*
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beta Catenin
Substances
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ARM protein, Drosophila
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Armadillo Domain Proteins
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CBY1 protein, human
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CTNNB1 protein, human
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Carrier Proteins
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Cby protein, Drosophila
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Cytoskeletal Proteins
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DNA-Binding Proteins
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Drosophila Proteins
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En protein, Drosophila
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Homeodomain Proteins
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LEF1 protein, human
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Lymphoid Enhancer-Binding Factor 1
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Nuclear Proteins
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Proto-Oncogene Proteins
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RNA, Messenger
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Trans-Activators
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Transcription Factors
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Ubx protein, Drosophila
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Wnt Proteins
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Wnt1 Protein
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Zebrafish Proteins
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beta Catenin
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wg protein, Drosophila
Associated data
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GENBANK/AE003736
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GENBANK/AK003719
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GENBANK/AL050345
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GENBANK/BI885798
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GENBANK/BJ093998