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

Ken Ichi Takemaru, Shinji Yamaguchi, Young Sik Lee, Yang Zhang, Richard W. Carthew, Randall T. Moon*

*Corresponding author for this work

Research output: Contribution to journalArticle

216 Scopus citations

Abstract

Inappropriate activation of downstream target genes by the oncoprotein β-catenin is implicated in development of numerous human cancers1,2. β-catenin and its fruitfly counterpart Armadillo act as a coactivator in the canonical Wnt/Wingless pathway by binding to Tcf/Lef transcription factors3-6. 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 β-catenin. In mammalian cultured cells we demonstrate that Chibby inhibits β-catenin-mediated transcriptional activation by competing with Lef-1 to bind to β-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.

Original languageEnglish (US)
Pages (from-to)905-909
Number of pages5
JournalNature
Volume422
Issue number6934
DOIs
StatePublished - Apr 24 2003

ASJC Scopus subject areas

  • General

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    Takemaru, K. I., Yamaguchi, S., Sik Lee, Y., Zhang, Y., Carthew, R. W., & Moon, R. T. (2003). Chibby, a nuclear β-catenin-associated antagonist of the Wnt/Wingless pathway. Nature, 422(6934), 905-909. https://doi.org/10.1038/nature01570