![]() SIAH proteins promote the ubiquitination and proteasomal degradation of Axin through interacting with a VxP motif in the GSK3-binding domain of Axin, and this function of SIAH is counteracted by GSK3 binding to Axin. Here, we identify SIAH1/2 (SIAH) as the E3 ligase mediating Wnt-induced Axin degradation. However, the underlying molecular mechanism and biological relevance of this targeting of Axin have not been elucidated. ![]() ![]() Wnt signaling itself promotes the degradation of Axin. Axin is a concentration-limiting factor responsible for the formation of the β-catenin destruction complex. The Wnt/β-catenin signaling pathway plays essential roles in embryonic development and adult tissue homeostasis.
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