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(American Journal of Pathology. 2003;163:2201-2209.)
© 2003 American Society for Investigative Pathology

Technical Advance

Reconstructed ß-Catenin/TCF4 Signaling in Yeast Applicable to Functional Evaluation of APC Mutations

Hidehisa Yamada^*, Keiji Furuuchi, Tetsuya Aoyama, Akihiko Kataoka, Jun-ichi Hamada, Mitsuhiro Tada, Shunichi Okushiba^*, Satoshi Kondo^*, Tetsuya Moriuchi and Hiroyuki Katoh^*

From the Department of Surgical Oncology,^* Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, the Division of Cancer-Related Genes, Research Section of Molecular Pathogenesis, Institute of Genetic Medicine, Hokkaido University, Sapporo, Japan; and the Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

In human genetics and molecular oncology, mutation research is necessary not only to identify mutations in nucleic acid sequences, but also to analyze the loss of function caused by mutant proteins. We reconstructed a protein-protein network system of human ß-catenin and TCF4, in Saccharomyces cerevisiae. ß-Catenin and TCF4 proteins form a complex and transactivate reporter genes. Co-expressed wild-type APC with ß-catenin and TCF4 inhibit the transcriptional activity of the ß-catenin/TCF4 complex in yeast, as well as in mammals. This unique method in which the ß-catenin/TCF4 signaling pathway is reconstructed in vivo may prove useful for the functional evaluation of APC mutants, including a type of APC truncated and missense mutants influenced to the ability of binding to ß-catenin.