Developing Strategies to Block Beta-Catenin Action in Signaling and Cell Adhesion During Carcinogenesis
Abstract
To understand cancer, we must first understand normal cell behavior. Drosophila Armadillo (Arm) and its human homolog beta-catenin are key players in adhesive junctions and in transduction of Wingless (Wg)/Wnt signals. Our working hypotheses are: 1) Several protein partners compete to bind Arm, and 2) Arm:dTCF activates Wg-responsive genes, while dTCF alone represses the same genes. Aim 1 is to understand how different partners compete with one another for binding Arm. Aim 2 focuses on how Arm and dTCF positively and negatively regulate Wg-responsive genes. In the past year we made significant progress. Aim 1. We used the two-hybrid system to further define the Arm binding site on DE-cadherin and extended our analysis of the effect of point mutations on binding. Our collaborators at the Weizmann Institute nearly completed a parallel analysis in mammalian cells, assessing the ability of cadherin-derived peptides to compete 13-catenin from its endogenous partners. Aim 2. Our analysis of the role of Arm's C-terminus was published in Genetics. We extended our study of Wg-responsive genes by examining the role of the chromatin remodeling protein Brahma: human Brahma was identified as a two-hybrid interactor with beta-catenin. Our preliminary data suggest that Brahma and Osa repress Wg-target genes.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA389734
Entities
People
- Mark A. Peifer
Organizations
- University of North Carolina at Chapel Hill