The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
The APC tumour suppressor has a nuclear export function
Abstract
The adenomatous polpyposis coli (APC) protein is mutated in most colorectal tumours. Nearly all APC mutations are truncations, and many of these terminate in the mutation cluster region located halfway through the protein. In cancer cells expressing mutant APC, beta-catenin is stabilized and translocates into the nucleus to act as a transcriptional co-activator of T-cell factor. During normal development, APC also promotes the destabilization of beta-catenin and Drosophila Armadillo. It does so by binding to the Axin complex which earmarks beta-catenin/Armadillo for degradation by the proteasome pathway. APC has a regulatory role in this process, which is poorly understood. Here we show that APC contains highly conserved nuclear export signals 3' adjacent to the mutation cluster region that enable it to exit from the nucleus. This ability is lost in APC mutant cancer cells, and we provide evidence that beta-catenin accumulates in the nucleus as a result. Thus, the ability of APC to exit from the nucleus appears to be critical for its tumour suppressor function.
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“As mentioned above, asymmetric membrane accumulation of Dsh is important for the non-canonical pathway and convergent extension movements.118–120”
From Wnt signal transduction pathways (2008) · cites this paper as [119]
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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
“β-catenin can also be actively transported back to the cytoplasm, by either an intrinsic export signal or as cargo of Axin (Cong and Varmus, 2004) or APC (Rosin-Arbesfeld et al., 2000) that shuttle between cytoplasm and nucleus.”
Wnt signal transduction pathways
Komiya, Y., & Habas, R. (2008) · Organogenesis · doi:10.4161/org.4.2.5851 · Cited by 1,528
Linking Colorectal Cancer to Wnt Signaling
Bienz, M., & Clevers, H. C. (2000) · Cell · doi:10.1016/s0092-8674(00)00122-7 · Cited by 1,518
Self-citationThe -Catenin Destruction Complex
Stamos, J. L., & Weis, W. I. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a007898 · Cited by 1,062
“Both Axin and APC contain CRM-1-dependent nuclear export signal sequences, and have been reported to mediate nuclear-cytoplasmic shuttling of b-catenin (Rosin-Arbesfeld et al. 2000; Henderson and Fagotto 2002; Cong and Varmus 2004).”
BackgroundBrabletz, T., Jung, A., Reu, S., Porzner, M., Hlubek, F., Kunz‐Schughart, L. A., Knuechel, R., & Kirchner, T. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.171610498 · Cited by 1,048
Metadata
- Authors
- Rosin-Arbesfeld, R., Townsley, F., & Bienz, M.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Corresponding author
- Bienz, Mariann
- ORCID
- Bienz, Mariann
- Venue
- Nature
- Published
- 2000-08
- Volume
- 406
- Issue
- 6799
- Pages
- 1009-1012
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1666932156
- Cited by
- 343
- References
- 30
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 1 · 2022: 7 · 2021: 4 · 2020: 6 · 2019: 4 · 2018: 8 · 2017: 4 · 2016: 6 · 2015: 6 · 2014: 7 · 2013: 12 · 2012: 10
- FWCI
- 15.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- nuclear export, nuclear export signal, β-catenin stabilization, colorectal cancer, proteasomal degradation, armadillos, mutation cluster region, tumor suppressor function
- MeSH terms
- Amino Acid Sequence, Animals, Biological Transport, Cell Nucleus, Cytoskeletal Proteins, Drosophila, Fatty Acids, Unsaturated, Multigene Family, Genetic Complementation Test, Humans, Molecular Sequence Data, Mutation, Peptide Fragments, Recombinant Fusion Proteins, Transfection, Tumor Cells, Cultured, Colorectal Neoplasms, Trans-Activators, Conserved Sequence, Genes, Reporter, COS Cells, Adenomatous Polyposis Coli Protein, beta Catenin
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