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 B-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. We made significant progress on both Aims. 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 Beta-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 p120 catenin binding. We characterized the role of TCF and Groucho in transcriptional repression of Wg-responsive genes. This work was published in Nature. We characterized the role of the C-terminus of Armadillo in transcriptional activation this work was published in Genetics.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA407492
Entities
People
- Mark A. Peifer
Organizations
- University of North Carolina at Chapel Hill