Wnt signaling: is the party in the nucleus?

  1. Karl Willert1 and
  2. Katherine A. Jones2,3
  1. 1 Department of Molecular and Cellular Medicine, University of California, San Diego, La Jolla, California 92093, USA;
  2. 2 Regulatory Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA

Abstract

The Wnt signaling pathway controls cell proliferation and body patterning throughout development. A surprising number of cytoplasmic Wnt regulators (e.g., β-catenin, Bcl-9/Lgs, APC, Axin) also appear, often transiently, in the nucleus. β-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 β-catenin destruction complex, yet also counteracts β-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 β-catenin enable a rapid coordination of gene expression and cytoskeletal organization throughout the cell in response to signaling.

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