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

Smalley, Matthew John ORCID: https://orcid.org/0000-0001-9540-1146, Fraser, Elizabeth, Paterson, Hugh, Naylor, Stuart, Cook, David, Jayatilake, Hiran, Fryer, Lee G., Hutchinson, Lisa, Fry, Michael J. and Dale, Trevor C. 1999. Interaction of Axin and Dvl-2 proteins regulates Dvl-2-stimulated TCF-dependent transcription. EMBO Journal 18 (10) , pp. 2823-2835. 10.1093/emboj/18.10.2823

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Abstract

Axin promotes the phosphorylation of β‐catenin by GSK‐3β, leading to β‐catenin degradation. Wnt signals interfere with β‐catenin turnover, resulting in enhanced transcription of target genes through the increased formation of β‐catenin complexes containing TCF transcription factors. Little is known about how GSK‐3β‐mediated β‐catenin turnover is regulated in response to Wnt signals. We have explored the relationship between Axin and Dvl‐2, a member of the Dishevelled family of proteins that function upstream of GSK‐3β. Expression of Dvl‐2 activated TCF‐dependent transcription. This was blocked by co‐expression of GSK‐3β or Axin. Expression of a 59 amino acid GSK‐3β‐binding region from Axin strongly activated transcription in the absence of an upstream signal. Introduction of a point mutation into full‐length Axin that prevented GSK‐3β binding also generated a transcriptional activator. When co‐expressed, Axin and Dvl‐2 co‐localized within expressing cells. When Dvl‐2 localization was altered using a C‐terminal CAAX motif, Axin was also redistributed, suggesting a close association between the two proteins, a conclusion supported by co‐immunoprecipitation data. Deletion analysis suggested that Dvl‐association determinants within Axin were contained between residues 603 and 810. The association of Axin with Dvl‐2 may be important in the transmission of Wnt signals from Dvl‐2 to GSK‐3β.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
Publisher:	European Molecular Biology Organization; Nature Publishing Group
ISSN:	0261-4189
Last Modified:	27 Oct 2022 09:09
URI:	https://orca.cardiff.ac.uk/id/eprint/64565

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