Negative regulation of Armadillo, a Wingless effector in Drosophila

Abstract

Drosophila Armadillo and its vertebrate homolog β-catenin play essential roles both in the transduction of Wingless/Wnt cell-cell signals and in the function of cell-cell adherens junctions. Wingless and Wnts direct numerous cell fate choices during development. We generated a mutant protein, ArmadilloS10, with a 54 amino acid deletion in its N-terminal domain. This mutant is con-stitutively active in Wingless signaling; its activity is inde-pendent of both Wingless signal and endogenous wild-type Armadillo. Armadillo’s role in signal transduction is normally negatively regulated by Zeste-white 3 kinase, which modulates Armadillo protein stability. ArmadilloS10 is more stable than wild-type Armadillo, suggesting that it is less rapidly targeted for degradation. We show that ArmadilloS10 has escaped from negative regulation by Zeste white-3 kinase, and thus accumulates outside junctions even in the absence of Wingless signal. Finally, we present data implicating kinases in addition to Zeste white-3 in Armadillo phosphorylation. We discuss two models for the negative regulation of Armadillo in normal development and discuss how escape from this regulation contributes to tumorigenesis.