Interactions between SOX factors and Wnt/β-catenin signaling in development and disease

The SOX family of transcription factors have emerged as modulators of canonical Wnt/β-catenin signaling in diverse development and disease contexts. There are over twenty SOX proteins encoded in the vertebrate genome and recent evidence suggests that many of these can physically interact with β-catenin and modulate the transcription of Wnt-target genes. The precise mechanisms by which SOX proteins regulate β-catenin/TCF activity are still being resolved and there is evidence to support a number of models including; protein-protein interactions, the binding of SOX factors to Wnt-target gene promoters, the recruitment of co-repressors or co-activators, modulation of protein stability and nuclear translocation. In some contexts Wnt signaling also regulates SOX expression resulting in feedback regulatory loops that fine tune cellular responses to β-catenin/TCF activity. In this review we summarize the examples of Sox-Wnt interactions and examine the underlying mechanisms of this potentially wide spread and underappreciated mode of Wnt-regulation