Journal
CELL CYCLE
Volume 9, Issue 18, Pages 3700-3709Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.9.18.13204
Keywords
Wnt signaling; ubiquitin; beta-catenin; dishevelled; signal transduction; protein degradation; cancer; development
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Funding
- Dutch Cancer Society [UU-2006-3508]
- University Utrecht
- European Research Council [242958]
- RUBICON EU network of excellence
- European Research Council (ERC) [242958] Funding Source: European Research Council (ERC)
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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/beta-catenin cascade, signaling events converge on the regulation of ubiquitin-mediated degradation of the crucial transcriptional regulator beta-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.
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