Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive 

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-1044

Hoffmans, R; Basler, K (2004). Identification and in vivo role of the Armadillo-Legless interaction. Development, 131(17):4393-4400.

[img]
Preview
PDF
605kB

Abstract

The Wnt signalling system controls many fundamental processes during animal development and its deregulation has been causally linked to colorectal cancer. Transduction of Wnt signals entails the association of beta-catenin with nuclear TCF DNA-binding factors and the subsequent activation of target genes. Using genetic assays in Drosophila, we have recently identified a presumptive adaptor protein, Legless (Lgs), that binds to beta-catenin and mediates signalling activity by recruiting the transcriptional activator Pygopus (Pygo). Here, we characterize the beta-catenin/Lgs interaction and show: (1) that it is critically dependent on two acidic amino acid residues in the first Armadillo repeat of beta-catenin; (2) that it is spatially and functionally separable from the binding sites for TCF factors, APC and E-cadherin; (3) that it is required in endogenous as well as constitutively active forms of beta-catenin for Wingless signalling output in Drosophila; and (4) that in its absence animals develop with the same phenotypic consequences as animals lacking Lgs altogether. Based on these findings, and because Lgs and Pygo have human homologues that can substitute for their Drosophila counterparts, we infer that the beta-catenin/Lgs binding site may thus serve as an attractive drug target for therapeutic intervention in beta-catenin-dependent cancer progression.

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
DDC:570 Life sciences; biology
Language:English
Date:September 2004
Deposited On:11 Feb 2008 12:20
Last Modified:27 Nov 2013 17:34
Publisher:Company of Biologists
ISSN:0950-1991
Publisher DOI:10.1242/dev.01296
PubMed ID:15294866
Citations:Web of Science®. Times Cited: 37
Google Scholar™

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page