SPring-8, the large synchrotron radiation facility

The Wnt signaling pathway has an essential role for various cell fates, such as embryonic development, cell differentiation, and proliferation. It has been known that inappropriate activation of this pathway causes the various human cancers. We have clarified the structure-function relationship of DIX domain of Axin and Dishevelled (Dvl2) which are involved in Wnt signaling pathway. We found that DIX domain of Dvl2 mediates reversible oligomerization, which is essential for the activity of the signaling. Crystal structure of Axin-DIX has been successfully determined. The DIX domain has a unique ubiquitin fold and polymerized in head-to-tail self-interaction fashion in the crystal. Mutagenesis studies based on the structure proved that the structure of DIX is an essential for the dynamic oligomerization of Dvl2. We propose that this dynamic oligomerization system is a basic principle in other signal transduction pathway.