Regulation of Wnt signaling by Sox proteins: XSox17 alpha/beta and XSox3 physically interact with beta-catenin.
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
A M
AM
Wellcome Trust/Cancer Research Campaign Institute of Cancer and Developmental Biology, Cambridge. amz@mole.bio.cam.ac.uk
Barish
G D
GD
Williams
B O
BO
Lavender
P
P
Klymkowsky
M W
MW
Varmus
H E
HE
D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011992:Endosomes / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism*; D006651:Histocytochemistry; D018398:Homeodomain Proteins / Q000235:genetics; D008845:Microinjections; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D055748:SOXB1 Transcription Factors; D055760:SOXF Transcription Factors; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D014981:Xenopus / Q000196:embryology; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
C495266:CTNNB1 protein, Xenopus; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C093133:SIA1 protein, Xenopus; D055748:SOXB1 Transcription Factors; D055760:SOXF Transcription Factors; C527788:Sox3 protein, Xenopus; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; C491603:sox17 protein, zebrafish; C491602:sox17a protein, Xenopus; C491601:sox17b.1 protein, Xenopus