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Control of β-Catenin Stability
Open accessAbstract
Regulation of beta-catenin degradation by intracellular components of the wnt pathway was reconstituted in cytoplasmic extracts of Xenopus eggs and embryos. The ubiquitin-dependent beta-catenin degradation in extracts displays a biochemical requirement for axin, GSK3, and APC. Axin dramatically accelerates while dishevelled inhibits beta-catenin turnover. Through another domain, dishevelled recruits GBP/Frat1 to the APC-axin-GSK3 complex. Our results confirm and extend models in which inhibition of GSK3 has two synergistic effects: (1) reduction of APC phosphorylation and loss of affinity for beta-catenin and (2) reduction of beta-catenin phosphorylation and consequent loss of its affinity for the SCF ubiquitin ligase complex. Dishevelled thus stabilizes beta-catenin, which can dissociate from the APC/axin complex and participate in transcriptional activation.
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“In the case of the activity CSM1 from Lee et al. (2003), several wet-lab data from their own experiments (WD1–WD5) as well as from Salic et al. (2000) [66] (WD1–WD3) are used during the calibration of the model SM1 which produces a Simulation Experiment SE1, the corresponding Simulation Data SD1 as well as the calibrated Simulation Model SM2.”
From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [66]
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Metadata
- Authors
- Salic, A., Lee, E., Mayer, L., & Kirschner, M. W.
- Affiliations
- Harvard University (US)
- Corresponding author
- Kirschner, Marc W.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2000-03
- Volume
- 5
- Issue
- 3
- Pages
- 523-532
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2069704514
- Cited by
- 335
- References
- 34
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 4 · 2021: 10 · 2020: 11 · 2019: 12 · 2018: 11 · 2017: 11 · 2016: 16 · 2015: 5 · 2014: 16 · 2013: 16 · 2012: 16
- FWCI
- 8.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- 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 stability, Wnt signaling, ubiquitin-mediated proteolysis, Axin, glycogen synthase kinase-3, APC, Dishevelled, SCF ubiquitin ligase, protein phosphorylation, Xenopus egg extracts, transcriptional activation
- MeSH terms
- Dishevelled Proteins, Animals, Carrier Proteins, Cell-Free System, Cytoplasm, Cytoskeletal Proteins, Models, Biological, Ovum, Phosphoproteins, Phosphorylation, Protein Binding, Proteins, Proto-Oncogene Proteins, Repressor Proteins, Subcellular Fractions, Ubiquitins, Xenopus, Trans-Activators, Protein Structure, Tertiary, Calcium-Calmodulin-Dependent Protein Kinases, Adenomatous Polyposis Coli Protein, Xenopus Proteins, Zebrafish Proteins, Glycogen Synthase Kinase 3, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Wnt Proteins, beta Catenin, Axin Protein
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