Interaction of axin and Dvl-2 proteins regulates Dvl-2-stimulated TCF-dependent transcription

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Updated: Oct 22, 2026

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
09:58

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis

Published on: June 27, 2020

M J Smalley1, E Sara, H Paterson

  • 1Developmental Biology, Section of Cell Biology and Experimental Pathology, Toby Robins Breakthrough Breast Cancer Research Centre, London, UK.

The EMBO Journal
|May 18, 1999
PubMed

Insights

Axin and Dishevelled-2 (Dvl-2) proteins interact, influencing beta-catenin turnover and TCF-dependent transcription in Wnt signaling pathways. This interaction is crucial for transmitting Wnt signals.

Area of Science:

  • Cellular biology
  • Molecular signaling pathways
  • Wnt signaling pathway

Background:

  • Axin facilitates beta-catenin phosphorylation by GSK-3beta, promoting degradation.
  • Wnt signals inhibit beta-catenin turnover, enhancing TCF transcription factor activity.
  • Regulation of GSK-3beta-mediated beta-catenin turnover by Wnt signals remains unclear.

Purpose of the Study:

  • To investigate the relationship between Axin and Dishevelled-2 (Dvl-2) in Wnt signaling.
  • To elucidate the role of Axin-Dvl-2 interaction in regulating beta-catenin turnover and transcription.

Main Methods:

  • Co-expression of Dvl-2, GSK-3beta, and Axin constructs in cells.
  • Analysis of TCF-dependent transcription.
  • Site-directed mutagenesis to disrupt GSK-3beta binding to Axin.
  • Co-localization studies using fluorescent tags.
  • Co-immunoprecipitation assays.
  • Deletion analysis to map Axin domains interacting with Dvl-2.

Main Results:

  • Dvl-2 expression activated TCF-dependent transcription, which was inhibited by GSK-3beta or Axin.
  • A GSK-3beta-binding region of Axin, or a mutated full-length Axin lacking GSK-3beta binding, acted as a transcriptional activator.
  • Axin and Dvl-2 co-localized in cells, and Dvl-2 altered Axin localization, indicating a close association.
  • The Dvl-2 association domain in Axin is located between residues 603 and 810.

Conclusions:

  • Axin and Dvl-2 interact physically and functionally.
  • This interaction is critical for Wnt signal transmission from Dvl-2 to GSK-3beta.
  • The Axin-Dvl-2 association influences beta-catenin turnover and TCF-mediated transcription.

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