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GBP, an inhibitor of GSK-3, is implicated in Xenopus development and oncogenesis

C Yost1, G H Farr, S B Pierce

  • 1Department of Biochemistry, University of Washington, Seattle 98195-7350, USA.

Cell
|July 11, 1998
PubMed

Insights

A novel protein, GBP, stabilizes beta-catenin in Xenopus embryos, which is essential for body axis formation. This discovery reveals a new Wnt-independent pathway crucial for embryonic development.

Area of Science:

  • Developmental biology
  • Molecular biology
  • Cell signaling

Background:

  • Beta-catenin accumulation on the dorsal side of early Xenopus embryos is critical for body axis formation.
  • Beta-catenin is stabilized dorsally through localized inhibition of the kinase Xgsk-3 via a Wnt ligand-independent mechanism.

Purpose of the Study:

  • To identify novel proteins involved in the Wnt-independent stabilization of beta-catenin.
  • To elucidate the role of these proteins in Xenopus embryonic axis formation.

Main Methods:

  • Two-hybrid screening to identify Xgsk-3 binding proteins.
  • In vivo phosphorylation assays to assess GBP's inhibitory function.
  • Ectopic expression and antisense oligonucleotide depletion to determine GBP's role in axis formation.

Main Results:

  • GBP, a maternal Xgsk-3-binding protein homologous to a T cell protooncogene, was identified.
  • GBP inhibits Xgsk-3 phosphorylation in vivo.
  • Ectopic GBP expression induced axis formation by stabilizing beta-catenin.
  • Depletion of maternal GBP mRNA disrupted dorsal-ventral axis establishment in Xenopus embryos.

Conclusions:

  • GBP is a key regulator of beta-catenin stabilization and is essential for Xenopus body axis formation.
  • GBP defines a family of GSK-3-binding proteins with significant roles in embryonic development and cell proliferation.

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