Destruction Complex Function in the Wnt Signaling Pathway of Drosophila Requires Multiple Interactions Between Adenomatous Polyposis Coli 2 and Armadillo

摘要: The tumor suppressor Adenomatous polyposis coli (APC) negatively regulates Wnt signaling through its activity in the destruction complex. APC binds directly to main effector of pathway, β-catenin (βcat, Drosophila Armadillo), and helps target it for degradation. In vitro studies demonstrated that a nonphosphorylated 20-amino-acid repeat (20R) βcat N-terminal extended region 20R. When phosphorylated, phospho-region an 20R also affinity is significantly increased. These distinct APC–βcat interactions suggest different models sequential steps complex activity. However, vivo role phosphorylation has not been rigorously tested. Here we investigated functional these molecular by making targeted mutations melanogaster APC2 disrupt deletion mutants missing Armadillo binding repeats. We tested ability regulate null APC1 double-null embryos. Overall, our data support APC2’s function, but plays more significant role. Furthermore, show 20Rs with homology vertebrate repeats have highest are functionally dispensable, contrary biochemical predictions. Finally, some mutants, function was dependent on APC1, suggesting may act cooperatively