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Regulation of Wnt signaling by Sox prote ... ally interact with beta-catenin
Regulation of Wnt signaling by Sox proteins: XSox17 alpha/beta and XSox3 physically interact with beta-catenin.
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Using a functional screen in Xenopus embryos, we identified a novel function for the HMG box protein XSox17 beta. Ectopic expression of XSox17 beta ventralizes embryos by inhibiting the Wnt pathway downstream of beta-catenin but upstream of the Wnt-responsive gene Siamois. XSox17 beta also represses transactivation of a TCF/LEF-dependent reporter construct by Wnt and beta-catenin. In animal cap experiments, it both activates transcription of endodermal genes and represses beta-catenin-stimulated expression of dorsal genes. The inhibition activity of XSox17 beta maps to a region C-terminal to the HMG box; this region of XSox17 beta physically interacts with the Armadillo repeats of beta-catenin. Two additional Sox proteins, XSox17 alpha and XSox3, likewise bind to beta-catenin and inhibit its TCF-mediated signaling activity. These results reveal an unexpected mechanism by which Sox proteins can modulate Wnt signaling pathways.
Zorn AM, Barish GD, Williams BO, Lavender P, Klymkowsky MW, Varmus HE
Molecular cell
1999-10-01 00:00
4
4
487-98
Animals,Cytoskeletal Proteins,DNA-Binding Proteins,Endosomes,Gene Expression Regulation, Developmental,High Mobility Group Proteins,Histocytochemistry,Homeodomain Proteins,Microinjections,Protein Binding,Proteins,Proto-Oncogene Proteins,RNA, Messenger,Repressor Proteins,Signal Transduction,Trans-Activators,Transcription Factors,Wnt Proteins,Xenopus,Xenopus Proteins,Zebrafish Proteins,beta Catenin,Cytoskeletal Proteins,DNA-Binding Proteins,High Mobility Group Proteins,Homeodomain Proteins,Proteins,Proto-Oncogene Proteins,RNA, Messenger,Repressor Proteins,Sox3 protein,Trans-Activators,Transcription Factors,Wnt Proteins,Xenopus Proteins,Xsox17-alpha protein, Xenopus,Xsox17-beta protein, Xenopus,Zebrafish Proteins,beta Catenin,beta-catenin protein, Xenopus,siamois protein, Xenopus,sox17 protein, zebrafish
Wellcome TrustCancer Research Campaign Institute of Cancer and Developmental Biology, Cambridge amzmolebiocamacuk
Mol. Cell
NIGMS GM54001
1097-2765
S1097-2765(00)80200-2
634
True
10549281
