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 and Randall T. Moon ()
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Ken-Ichi Takemaru: University of Washington School of Medicine
Shinji Yamaguchi: Northwestern University
Young Sik Lee: Northwestern University
Yang Zhang: University of Washington School of Medicine
Richard W. Carthew: Northwestern University
Randall T. Moon: University of Washington School of Medicine

Nature, 2003, vol. 422, issue 6934, 905-909

Abstract: 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 factors3,4,5,6. 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.

Date: 2003
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DOI: 10.1038/nature01570

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