The thioredoxin-related redox-regulating protein nucleoredoxin inhibits Wnt-beta-catenin signalling through dishevelled

Nat Cell Biol. 2006 May;8(5):501-8. doi: 10.1038/ncb1405. Epub 2006 Apr 2.


Dishevelled (Dvl) transduces signals from the Wnt receptor, Frizzled, to downstream components, leading to the stabilization of beta-catenin and subsequent activation of the transcription factor T cell factor (TCF) and/or lymphoid enchancer factor (LEF). However, the mechanism of Dvl action remains unclear. Here, we report that nucleoredoxin (NRX), a thioredoxin (TRX) family protein, interacts with Dvl. Overexpression of NRX selectively suppresses the Wnt-beta-catenin pathway and ablation of NRX by RNA-interference (RNAi) results in activation of TCF, accelerated cell proliferation and enhancement of oncogenicity through cooperation with mitogen-activated extracellular signal regulated kinase kinase (MEK) or Ras. We find that cells respond to H(2)O(2) stimulation by activating TCF. Redox-dependent activation of the Wnt-beta-catenin pathway occurs independently of extracellular Wnts and is impaired by RNAi of NRX . In addition, association between Dvl and NRX is inhibited by H(2)O(2) treatment. These data suggest a relationship between the Wnt-beta-catenin pathway and redox signalling through redox-sensitive association of NRX with Dvl.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • COS Cells
  • Cell Proliferation
  • Cells, Cultured
  • Chlorocebus aethiops
  • Culture Media, Conditioned
  • Dishevelled Proteins
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / embryology
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Mice
  • NIH 3T3 Cells
  • Nuclear Proteins / metabolism*
  • Oxidation-Reduction
  • Oxidoreductases / metabolism*
  • Phosphoproteins / metabolism*
  • Protein Binding
  • RNA Interference
  • Signal Transduction*
  • TCF Transcription Factors / metabolism
  • Thioredoxins / metabolism*
  • Transcriptional Activation / drug effects
  • Wnt Proteins / antagonists & inhibitors*
  • Xenopus
  • Xenopus Proteins
  • beta Catenin / antagonists & inhibitors*


  • Adaptor Proteins, Signal Transducing
  • Culture Media, Conditioned
  • DVL1 protein, Xenopus
  • Dishevelled Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • TCF Transcription Factors
  • Wnt Proteins
  • Xenopus Proteins
  • beta Catenin
  • Thioredoxins
  • Hydrogen Peroxide
  • Oxidoreductases
  • nucleoredoxin