The various roles of ubiquitin in Wnt pathway regulation.

Wnt signaling mediates key developmental and homeostatic processes including stem cell maintenance, growth and cell fate specification, cell polarity and migration. Inappropriate activation of Wnt signaling is linked to a range of human disorders, most notably cancer and neurodegenerative diseases. In the Wnt/β-catenin cascade, signaling events converge on the regulation of ubiquitin-mediated degradation of the crucial transcriptional regulator β-catenin. The emerging mechanisms by which ubiquitin modification of proteins controls cellular pathways comprise both proteolytic and nonproteolytic functions. In nonproteolytic functions, ubiquitin acts as a signaling device in the control of protein activity, subcellular localization and complex formation. Here, we review and discuss recent developments that implicate ubiquitin-mediated mechanisms at multiple steps of Wnt pathway activation.