Wnt signaling: is the party in the nucleus?

Abstract

The Wnt signaling pathway controls cell proliferation and body patterning throughout development. A surprising number of cytoplasmic Wnt regulators (e.g., beta-catenin, Bcl-9/Lgs, APC, Axin) also appear, often transiently, in the nucleus. beta-Catenin is an integral component of E-cadherin complexes at intercellular adherens junctions, but also recruits chromatin remodeling complexes to activate transcription in the nucleus. The APC tumor suppressor is a part of the cytoplasmic beta-catenin destruction complex, yet also counteracts beta-catenin transactivation and histone H3K4 methylation at Wnt target genes. Furthermore, APC coordinates the cyclic exchange of Wnt coregulator complexes at the DNA. These opposing roles of APC and beta-catenin enable a rapid coordination of gene expression and cytoskeletal organization throughout the cell in response to signaling.