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 language | English |
|---|---|
| Pages (from-to) | 905-909 |
| Number of pages | 5 |
| Journal | Nature |
| Volume | 422 |
| Issue number | 6934 |
| DOIs | |
| Publication status | Published - 2003 Apr 24 |
| Externally published | Yes |
Bibliographical note
Funding Information:Acknowledgements We thank R. Holmgren, R. Pestell, M. Waterman and DSHB for reagents; M. Peifer, J. Treisman and Bloomington Stock Center for fly stocks; R. Holmgren, F.-Q. Li and members of the Carthew and Moon laboratories for critically reading the manuscript. This work was supported by postdoctoral fellowships from the Japan Science and Technology Corporation and Uehara Memorial Foundation (to K.-I.T.), the Pew Charitable Trust (to R.W.C.), and by an NIH grant (to R.T.M.). R.T.M. is an Investigator of the Howard Hughes Medical Institute.
ASJC Scopus subject areas
- General
