The SIAH E3 ubiquitin ligases promote Wnt/β-catenin signaling through mediating Wnt-induced Axin degradation.
Lei Ji et al., Genes & Development 2017, vol.31, 904–915
In this paper, authors demonstrate that an E3 ligase (IAH1/2 or SIAH) initiates a positive feedback loop to maintain activation of Wnt signaling. SIAH interacts with a VxP motif in Axin that is located within the GSK3-binding domain of the protein. Upon initial activation of Wnt signaling, Axin dissociates from the destruction complex, making it accessible to SIAH-mediated ubiquitination and degradation. This sets a feed-forward mechanism leading to sustained activation of the pathway.