Abstract
Using a functional screen in Xenopus embryos, we identified a novel function for the HMG box protein XSox17β. Ectopic expression of XSox17β ventralizes embryos by inhibiting the Wnt pathway downstream of β-catenin but upstream of the Wnt-responsive gene Siamois. XSox17β also represses transactivation of a TCF/LEF-dependent reporter construct by Wnt and β-catenin. In animal cap experiments, it both activates transcription of endodermal genes and represses β-catenin-stimulated expression of dorsal genes. The inhibition activity of XSox17β maps to a region C-terminal to the HMG box; this region of XSox17β physically interacts with the Armadillo repeats of β-catenin. Two additional Sox proteins, XSox17α and XSox3, likewise bind to β-catenin and inhibit its TCF-mediated signaling activity. These results reveal an unexpected mechanism by which Sox proteins can modulate Wnt signaling pathways.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 487-498 |
| Number of pages | 12 |
| Journal | Molecular cell |
| Volume | 4 |
| Issue number | 4 |
| DOIs | |
| State | Published - Oct 1999 |
Funding
We thank Paul Robbins, Rudolf Grosschedl, Hans Clevers, Bert Vogelstein, Doug Melton, Tony Kouzarides, Hugh Woodland, Rob Grainger, and Randy Moon for generously providing DNA constructs. A. M. Z. thanks J. B. Gurdon for encouragement and support and D. Niranjin for help with the expression screen. We also thank M. Chamorro, J. M. Li, M. Erdos, S. Lipkin, and T. Kouzarides for technical advice and helpful discussions and T. Wynshaw-Boris, G. Fisher, and F. Stennard for critical readings of this manuscript. G. D. B. is a Howard Hughes Medical Institute National Institutes of Health Research Scholar. B. O. W. is a fellow of the Damon Runyon–Walter Winchell Cancer Research Fund. M. W. K. was supported by NIH grant GM54001. This work was supported by grants from the Cancer Research Campaign (UK) and the Wellcome Trust to A. M. Z.
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology