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Chibby, a nuclear b-catenin-associated antagonist of the Wnt/Wingless pathway.
- Source :
- Nature; 4/24/2003, Vol. 422 Issue 6934, p905, 5p
- Publication Year :
- 2003
-
Abstract
- Inappropriate activation of downstream target genes by the oncoprotein ?-catenin is implicated in development of numerous human cancers. ?-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 ?-catenin. In mammalian cultured cells we demonstrate that Chibby inhibits ?-catenin-mediated transcriptional activation by competing with Lef-1 to bind to ?-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. [ABSTRACT FROM AUTHOR]
- Subjects :
- PROTEINS
DROSOPHILIDAE
RNA
CHEMICAL inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 00280836
- Volume :
- 422
- Issue :
- 6934
- Database :
- Complementary Index
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 9585023
- Full Text :
- https://doi.org/10.1038/nature01570