Molecular Mechanisms And Biological Functions Of Wnt Signaling

Secreted Wnt protein is highly conserved in evolution, and plays the important roles in embrogenesis and tumorgenesis. Its signal pathways determine or regulate multiple cell functions such as proliferation, differentiation, polarity, apoptosis and survival in embryonic development and in adult stage. Misregulation of Wnt signaling is tightly correlated to many human diseases, such as colon cancer and Alzheimer's disease. In briefly established Wnt signal pathway, Wnt signal mianly transduces on the basis of protein-protein interaction. After establish a stable yeast two-hybrid system, we use it on the discovery and research of Wnt signal pathway/network. Among the large-scale screening using a series of Wnt signaling pathway related proteins as baits in our lab, I did the screening with 11 baits, and got more than 1000 positive clones, which contain 294 interactions and 259 cDNAs. There are more than 10 interactions have been reported in previously published paper with the study on biological function. Furthermore, there are 22 proteins were found to bind several "baits"in our yeast two-hybrid screening, in other words, we found 22 potential protein complex. Combine all the information; we can briefly construct the interaction network of Wnt signal pathway. Among this network, some interactions were obviously related to the regulatory mechanism of canonical Wnt pathway and noncanonical Wnt pathway, and others may play the roles in the biological function of Wnt pathway. The functions of the several interactions in this network have been revealed, and more research work is still in the process. In the second and the third part of this thesis, we mainly discussed the biological function of the interaction between the main transducer of the canonical Wnt pathway, β-catenin and inhibitor of MyoD family a (I-mfa). I-mfa was reported previously not only to interact with myogenic related factors (MRFs), but also to be a partner of the transcription factor, LEF1/TCF, and to suppress their transcriptional activity. We found that β-catenin...