1. ¹Department of Biochemistry, University of Washington, Seattle, WA, USA
2. ²Department Biological Structure, University of Washington, Seattle, WA, USA

Correspondence: Professor D Kimelman, Department of Biochemistry, University of Washington, Box 357350, Seattle, WA 98195-7350, USA. E-mail: kimelman@u.washington.edu

Abstract

At the heart of the canonical Wnt signaling pathway is the -catenin destruction complex, which functions in the absence of Wnt signaling to keep the cytosolic and nuclear levels of -catenin very low by promoting the phosphorylation and ubiquitination of -catenin. Structural studies, combined with other experimental approaches, have begun to provide important insights into the mechanism of the destruction complex. We suggest a working model for the destruction complex based on the existing structural and experimental data, and focus on the questions that this model and other studies have raised about the function of the complex in both the normal and Wnt-inhibited states.