RGD Reference Report - Inhibition of Wnt signaling pathway by a novel axin-binding protein. - Rat Genome Database

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Inhibition of Wnt signaling pathway by a novel axin-binding protein.

Authors: Kadoya, T  Kishida, S  Fukui, A  Hinoi, T  Michiue, T  Asashima, M  Kikuchi, A 
Citation: Kadoya T, etal., J Biol Chem 2000 Nov 24;275(47):37030-7.
RGD ID: 1299408
Pubmed: (View Article at PubMed) PMID:10944533
DOI: Full-text: DOI:10.1074/jbc.M005984200

Axin forms a complex with adenomatous polyposis coli gene product, glycogen synthase kinase-3beta (GSK-3beta), beta-catenin, Dvl, and protein phosphatase 2A and functions as a scaffold protein in the Wnt signaling pathway. In the Axin complex, GSK-3beta efficiently phosphorylates beta-catenin, which is then ubiquitinated and degraded by proteasome. We isolated a novel protein that binds to Axin and named it Axam (for Axin associating molecule). Axam formed a complex with Axin in intact cells and bound directly to Axin. Axam inhibited the complex formation of Dvl with Axin and the activity of Dvl to suppress GSK-3beta-dependent phosphorylation of Axin. Furthermore, Axam induced the degradation of beta-catenin in SW480 cells and inhibited Wnt-dependent axis duplication in Xenopus embryos. These results suggest that Axam regulates the Wnt signaling pathway negatively by inhibiting the binding of Dvl to Axin.


Gene Ontology Annotations    

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Axin1  (axin 1)
Senp2  (SUMO specific peptidase 2)

Additional Information