Reconstructed beta-catenin/TCF4 signaling in yeast applicable to functional evaluation of APC mutations.
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 beta-catenin and TCF4, in Saccharomyces cerevisiae. beta-Catenin and TCF4 proteins form a complex and transactivate reporter genes. Co-expressed wild-type APC with beta-catenin and TCF4 inhibit the transcriptional activity of the beta-catenin/TCF4 complex in yeast, as well as in mammals. This unique method in which the beta-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 beta-catenin.
Yamada
Hidehisa
H
Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Furuuchi
Keiji
K
Aoyama
Tetsuya
T
Kataoka
Akihiko
A
Hamada
Jun-ichi
J
Tada
Mitsuhiro
M
Okushiba
Shunichi
S
Kondo
Satoshi
S
Moriuchi
Tetsuya
T
Katoh
Hiroyuki
H
D015179:Colorectal Neoplasms / Q000175:diagnosis; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D017491:Genes, APC; D006801:Humans; D009154:Mutation / Q000502:physiology*; D020125:Mutation, Missense / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D015398:Signal Transduction; D051820:TCF Transcription Factors; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D051176:beta Catenin