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Crystal structure of a β-catenin/Axin complex suggests a mechanism for the β-catenin destruction complex
Open accessAbstract
The “β-catenin destruction complex” is central to canonical Wnt/β-catenin signaling. The scaffolding protein Axin and the tumor suppressor adenomatous polyposis coli protein (APC) are critical components of this complex, required for rapid β-catenin turnover. We determined the crystal structure of a complex between β-catenin and the β-catenin-binding domain of Axin (Axin-CBD). The Axin-CBD forms a helix that occupies the groove formed by the third and fourth armadillo repeats of β-catenin and thus precludes the simultaneous binding of other β-catenin partners in this region. Our biochemical studies demonstrate that, when phosphorylated, the 20-amino acid repeat region of APC competes with Axin for binding to β-catenin. We propose that a key function of APC in the β-catenin destruction complex is to remove phosphorylated β-catenin product from the active site.
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Wnt/β-Catenin Signaling in Development and Disease
Clevers, H. (2006) · Cell · doi:10.1016/j.cell.2006.10.018 · Cited by 5,568
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Wnt/β-Catenin Signaling: Components, Mechanisms, and Diseases
MacDonald, B. T., Tamai, K., & He, X. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.06.016 · Cited by 5,583
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“There are now crystallographic structures of Axin contacting β-catenin (Xing et al. 2003) and Axin bound to APC (Spink et al. 2000).”
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Wnt signalling and its impact on development and cancer
Klaus, A., & Birchmeier, W. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2389 · Cited by 1,595
Metadata
- Authors
- Xing, Y., Clements, W. K., Kimelman, D., & Xu, W.
- Affiliations
- University of Washington (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2003-01-01
- Volume
- 17
- Issue
- 22
- Pages
- 2753-2764
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC280624
- OpenAlex
- W2041827225
- Semantic Scholar
- f02d1678de9728664b949b5fed44792fbdcc704e
- Cited by
- 237
- References
- 50
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 10 · 2023: 9 · 2022: 15 · 2021: 9 · 2020: 10 · 2019: 11 · 2018: 7 · 2017: 10 · 2016: 7 · 2015: 9 · 2014: 16 · 2013: 12 · 2012: 14
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (CA 90351, R01CA090351)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD027262, HD27262)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- β-catenin, Axin, β-catenin destruction complex, Wnt/β-catenin signaling, adenomatous polyposis coli, armadillo repeats, protein-protein complex structure, β-catenin phosphorylation, protein turnover, tumor suppressor
- MeSH terms
- Amino Acid Sequence, Animals, Binding Sites, Cytoskeletal Proteins, Humans, Models, Molecular, Molecular Sequence Data, Phosphorylation, Protein Binding, Protein Conformation, Proteins, Repressor Proteins, Xenopus laevis, Signal Transduction, Trans-Activators, Sequence Homology, Amino Acid, Crystallography, X-Ray, Adenomatous Polyposis Coli Protein, Xenopus Proteins, beta Catenin, Axin Protein
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