Xom induces proteolysis of β-catenin through GSK3β-mediated pathway

FEBS Lett. 2018 Feb;592(3):299-309. doi: 10.1002/1873-3468.12949. Epub 2017 Dec 27.

Abstract

The dorsal cell fate determination factor β-catenin and its antagonist, the ventral cell fate determination factor Xom, are expressed and distributed in a polarized fashion during early vertebrate embryogenesis. Ubiquitin-mediated proteolysis has been shown to control the abundance of both β-catenin and Xom. However, the mechanism of ubiquitin-mediated proteolysis in regulating dorsoventral patterning remains largely unclear. Our current study shows that Xom induces proteolysis of β-catenin through GSK3-mediated phosphorylation of Ser33/37 of β-catenin. Our findings reveal a novel pathway that regulates β-catenin stability, and suggest, for the first time, a critical function of ubiquitin-mediated proteolysis in balancing the integration of dorsal-ventral signals and the polarized distribution of β-catenin and Xom during dorsoventral axis formation.

Keywords: GSK; Wnt; proteolysis.

Publication types

  • Letter
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Body Patterning
  • Cell Differentiation
  • Cell Line
  • Glycogen Synthase Kinase 3 / metabolism*
  • Homeodomain Proteins / metabolism*
  • Humans
  • Phosphorylation
  • Protein Stability
  • Proteolysis
  • Serine / chemistry
  • Signal Transduction
  • Transcription Factors / metabolism*
  • Ubiquitin / metabolism
  • Xenopus / growth & development*
  • Xenopus / metabolism
  • Xenopus Proteins / chemistry*
  • Xenopus Proteins / metabolism*
  • beta Catenin / chemistry*

Substances

  • CTNNB1 protein, Xenopus
  • Homeodomain Proteins
  • Transcription Factors
  • Ubiquitin
  • Xenopus Proteins
  • beta Catenin
  • ventx2.1 protein, Xenopus
  • Serine
  • GSK3B protein, Xenopus
  • Glycogen Synthase Kinase 3