The DOI matches its Crossref record; 72 of the 72 references it cites were found in a registry or an index.
β-Catenin destruction complex: insights and questions from a structural perspective
Abstract
At the heart of the canonical Wnt signaling pathway is the beta-catenin destruction complex, which functions in the absence of Wnt signaling to keep the cytosolic and nuclear levels of beta-catenin very low by promoting the phosphorylation and ubiquitination of beta-catenin. Structural studies, combined with other experimental approaches, have begun to provide important insights into the mechanism of the destruction complex. We suggest a working model for the destruction complex based on the existing structural and experimental data, and focus on the questions that this model and other studies have raised about the function of the complex in both the normal and Wnt-inhibited states.
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In the citing paper
“Next, the β-catenin proteins undergo proteasomal destruction [259, 260], which is greatly accelerated by the presence of IDRs in addition to the bound ubiquitin signal [262].”
From Intrinsically disordered proteins play diverse roles in cell signaling (2022) · cites this paper as [260]
In the citing paper
“Prior to Wnt signaling, the transcription factor β-catenin is maintained at low levels by the β-catenin destruction complex, which is an assembly of the 852 residue mostly disordered scaffold protein axin, the 2,843 residue massively disordered protein adenomatous polyposis coli (APC), and the three mostly structured proteins β-catenin, casein kinase Ia (CKI-a), and glycogen synthetase kinase 3b (”
From Intrinsically disordered proteins play diverse roles in cell signaling (2022) · cites this paper as [260]
In the citing paper
“The two kinases phosphorylate residues within a long IDR at β-catenin’s amino terminus [259, 260].”
From Intrinsically disordered proteins play diverse roles in cell signaling (2022) · cites this paper as [260]
Citations
Cites
The Wnt Signaling Pathway in Development and Disease
Logan, C. Y., & Nusse, R. (2004) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.20.010403.113126 · Cited by 5,325
Wnt signalling in stem cells and cancer
Reya, T., & Clevers, H. (2005) · Nature · doi:10.1038/nature03319 · Cited by 3,666
Control of β-Catenin Phosphorylation/Degradation by a Dual-Kinase Mechanism
Liu, C., Li, Y., Semënov, M. V., Han, C., Baeg, G., Tan, Y., Zhang, Z., Lin, X., & He, X. (2002) · Cell · doi:10.1016/s0092-8674(02)00685-2 · Cited by 2,152
WNT and β-catenin signalling: diseases and therapies
Moon, R. T., Kohn, A. D., Ferrari, G. V. D., & Kaykas, A. (2004) · Nature Reviews Genetics · doi:10.1038/nrg1427 · Cited by 1,763
Cohen, P., & Frame, S. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35096075 · Cited by 1,493
Ikeda, S., Kishida, S., Yamamoto, H., Murai, H., Koyama, S., & Kikuchi, A. (1998) · The EMBO Journal · doi:10.1093/emboj/17.5.1371 · Cited by 1,248
Mao, J., Wang, J., Liu, B., Pan, W., Farr, G. H., Flynn, C., Yuan, H., Takada, S., Kimelman, D., Li, L., et al. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00224-6 · Cited by 839 · cited 4×
“For example, as discussed above, under certain conditions LRP5/6 can function in a Frizzled and Dishevelled-independent manner whereas normally all of these components function synergistically (Li et al., 2002; Schweizer and Varmus, 2003; Cong et al., 2004b).”
BackgroundInfluentialSelf-citationAxin-mediated CKI phosphorylation of β-catenin at Ser 45: a molecular switch for the Wnt pathwayPreprint
Amit, S., Hatzubai, A., Birman, Y., Andersen, J., Ben-Shushan, E., Mann, M., Ben‐Neriah, Y., & Alkalay, I. (2002) · Genes & Development · doi:10.1101/gad.230302 · Cited by 784
Huber, A. H., & Weis, W. I. (2001) · Cell · doi:10.1016/s0092-8674(01)00330-0 · Cited by 777
Three-Dimensional Structure of the Armadillo Repeat Region of β-Catenin
Huber, A. H., Nelson, W. J., & Weis, W. I. (1997) · Cell · doi:10.1016/s0092-8674(00)80352-9 · Cited by 727
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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
The many faces and functions of β‐catenin
Valenta, T., Hausmann, G., & Basler, K. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.150 · Cited by 1,598
“The scaffold establishes a platform for associated kinases to phosphorylate b -catenin (Kimelman and Xu, 2006; Roberts et al , 2011).”
InfluentialProximal events in Wnt signal transduction
Angers, S., & Moon, R. T. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2717 · Cited by 1,135
Wnt Signaling through Inhibition of β-Catenin Degradation in an Intact Axin1 Complex
Li, V. S. W., Ng, S. S., Boersema, P. J., Low, T. Y., Karthaus, W. R., Gerlach, J. P., Mohammed, S., Heck, A. J. R., Maurice, M. M., Mahmoudi, T., et al. (2012) · Cell · doi:10.1016/j.cell.2012.05.002 · Cited by 889
GSK3: a multifaceted kinase in Wnt signaling
Wu, D., & Pan, W. (2009) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2009.10.002 · Cited by 862
Metadata
- Authors
- Kimelman, D., & Xu, W.
- Affiliations
- University of Washington (US)
- Corresponding author
- Kimelman, D
- ORCID
- Venue
- Oncogene
- Published
- 2006-12-04
- Volume
- 25
- Issue
- 57
- Pages
- 7482-7491
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2072335762
- Cited by
- 628
- References
- 72
- Citations by year
- 2026: 8 · 2025: 21 · 2024: 23 · 2023: 27 · 2022: 41 · 2021: 52 · 2020: 19 · 2019: 25 · 2018: 37 · 2017: 40 · 2016: 28 · 2015: 36 · 2014: 51 · 2013: 33 · 2012: 40
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (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 destruction complex, Wnt/β-catenin signaling, β-catenin phosphorylation, β-catenin ubiquitination, protein complex structure, Wnt signaling inhibition
- MeSH terms
- Animals, Cell Nucleus, Colonic Neoplasms, Cytosol, Humans, Models, Biological, Phosphorylation, Protein Conformation, Stem Cells, Ubiquitin, beta Catenin
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