Regulation of Wnt Signaling by Sox Proteins: XSox17 alpha/beta and XSox3 Physically Interact With Beta-Catenin

Mol Cell. 1999 Oct;4(4):487-98. doi: 10.1016/s1097-2765(00)80200-2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cytoskeletal Proteins / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Endosomes / genetics
  • Gene Expression Regulation, Developmental
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / metabolism*
  • Histocytochemistry
  • Homeodomain Proteins / genetics
  • Microinjections
  • Protein Binding
  • Proteins / genetics
  • Proteins / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Messenger / metabolism
  • Repressor Proteins / metabolism
  • SOXB1 Transcription Factors
  • SOXF Transcription Factors
  • Signal Transduction*
  • Trans-Activators*
  • Transcription Factors*
  • Wnt Proteins
  • Xenopus / embryology
  • Xenopus Proteins*
  • Zebrafish Proteins*
  • beta Catenin

Substances

  • CTNNB1 protein, Xenopus
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Homeodomain Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Repressor Proteins
  • SIA1 protein, Xenopus
  • SOXB1 Transcription Factors
  • SOXF Transcription Factors
  • Sox3 protein, Xenopus
  • Trans-Activators
  • Transcription Factors
  • Wnt Proteins
  • Xenopus Proteins
  • Zebrafish Proteins
  • beta Catenin
  • sox17 protein, zebrafish
  • sox17a protein, Xenopus
  • sox17b.1 protein, Xenopus