Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Nature. 2003 Apr 24;422(6934):905-9.

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

Author information

  • 1Howard Hughes Medical Institute, Room K536C Health Sciences Building, Campus Box 357750, Department of Pharmacology, and Center for Developmental Biology, University of Washington School of Medicine, Seattle, Washington 98195, USA.

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.

PMID:
12712206
[PubMed - indexed for MEDLINE]

Publication Types, MeSH Terms, Substances, Secondary Source ID

Publication Types

MeSH Terms

Substances

Secondary Source ID

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for Faculty of 1000
    Loading ...
    Write to the Help Desk