Reconstituting regulation of the canonical Wnt pathway by engineering a minimal β-catenin destruction machine.

ABSTRACT: Negatively regulating key signaling pathways is critical to development and altered in cancer. Wnt signaling is kept off by the destruction complex, which is assembled around the tumor suppressors APC and Axin and targets β-catenin for destruction. Axin and APC are large proteins with many domains and motifs that bind other partners. We hypothesized that if we identified the essential regions required for APC:Axin cooperative function and used these data to design a minimal β-catenin-destruction machine, we would gain new insights into the core mechanisms of destruction complex function. We identified five key domains/motifs in APC or Axin that are essential for their function in reconstituting Wnt regulation. Strikingly, however, certain APC and Axin mutants that are nonfunctional on thei

SUBMITTER: Pronobis MI 

PROVIDER: S-EPMC5221518 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature