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 13-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. 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 completed a parallel analysis in mammalian cells, assessing the ability of cadherin-derived peptides to compete 13-catenin from its endogenous partners. This work was published in Molecular Biology of the Cell. We have also introduced into transgenic flies mutant versions of DE-cadherin which should specifically block Arm or pl20catenin binding.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA398037
Entities
People
- Mark Peifer
Organizations
- University of North Carolina at Chapel Hill