WNT SIGNALING Wnt signaling: Sox Enters the Wnt Pathway

Abstract: The Wnt signaling pathway regulates numerous cellular responses including those that govern axis formation and dorsal-ventral patterning in the developing Xenopus laevis embryo. Upon binding to its receptor Frizzled, a signaling cascade is triggered that results in ß-catenin-dependent transcription of Wnt target genes. The TCF family of DNA-binding proteins are known nuclear effectors of Wnt signaling. Zorn et al. report that the Sox family of DNA-binding proteins inhibits the Wnt pathway in Xenopus. Ectopic expression of Sox repressed Wnt and ß-catenin-stimulated transcription from a TCF-dependent reporter gene. Although Sox and TCF did not compete for the same DNA-binding site, the two proteins did compete for binding to ß-catenin. The authors further determined that binding sites for Sox and TCF on ß-catenin overlap. Overexpression of Sox inhibited expression of the endogenous Wnt target gene Siamois, but also stimulated expression of an endogenous endodermal gene. The authors suggest that Sox binds to ß-catenin or to a ß-catenin-TCF complex and inhibits Wnt signaling, which may be important for endoderm development. However, it is not clear as to whether Sox proteins are normally involved in axis formation.

Zorn, A.M., Barish, G.D., Williams, B.O., Lavender, O., Klymkowsky, M.W., and Varmus, H.E. (1999) Regulation of Wnt signaling by Sox proteins: XSox17/ß and XSox3 physically interact with ß-catenin. Mol. Cell 4: 487-498. [Online Journal]