Cited by 337Wnt/β-catenin signaling in development and cancerSignaling Pathways in DiseaseUbiquitin and proteasome pathways

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Control of β-Catenin Stability

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Salic, Adrian, Lee, Ethan, Mayer, Leslie, Kirschner, Marc W.·2000·Molecular Cell

DOI 10.1016/s1097-2765(00)80446-3

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Abstract

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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Authors: Salic, A., Lee, E., Mayer, L., & Kirschner, M. W.
Affiliations: Harvard University (US)
Corresponding author: Kirschner, Marc W.
ORCID: Salic, Adrian
Lee, Ethan
Kirschner, Marc W.
Venue: Molecular Cell
Publisher: Elsevier BV
Published: 2000-03
Volume: 5
Issue: 3
Pages: 523-532
ISSN: 1097-2765 (ISSN-L)
DOI: 10.1016/s1097-2765(00)80446-3
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 4886 d)
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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