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- Title
Chibby, a nuclear beta-catenin-associated antagonist of the Wnt/Wingless pathway.
- Authors
Takemaru, Ken-Ichi; Yamaguchi, Shinji; Lee, Young Sik; Zhang, Yang; Carthew, Richard W; Moon, Randall T
- 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
Nature, 2003, Vol 422, Issue 6934, p905
- ISSN
0028-0836
- Publication type
Journal Article
- DOI
10.1038/nature01570