Chibby, a nuclear beta-catenin-associated antagonist of the Wnt/Wingless pathway.

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.
Mesh Terms:
Animals, Armadillo Domain Proteins, Binding Sites, COS Cells, Carrier Proteins, Cell Line, Conserved Sequence, Cytoskeletal Proteins, DNA-Binding Proteins, Drosophila Proteins, Drosophila melanogaster, Epistasis, Genetic, Homeodomain Proteins, Humans, Lymphoid Enhancer-Binding Factor 1, Molecular Sequence Data, Nuclear Proteins, Phenotype, Protein Binding, Proto-Oncogene Proteins, RNA Interference, RNA, Messenger, Signal Transduction, Trans-Activators, Transcription Factors, Transcriptional Activation, Wnt Proteins, Wnt1 Protein, Zebrafish Proteins, beta Catenin
Nature
Date: Apr. 24, 2003
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