Cited by 343Wnt/β-catenin signaling in development and cancerGenetic factors in colorectal cancerSignaling Pathways in Disease

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The APC tumour suppressor has a nuclear export function

Rosin-Arbesfeld, Rina, Townsley, Fiona, Bienz, Mariann·2000·Nature

DOI 10.1038/35023016

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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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Authors: Rosin-Arbesfeld, R., Townsley, F., & Bienz, M.
Affiliations: MRC Laboratory of Molecular Biology (GB)
Corresponding author: Bienz, Mariann
ORCID: Bienz, Mariann
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2000-08
Volume: 406
Issue: 6799
Pages: 1009-1012
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/35023016
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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The APC tumour suppressor has a nuclear export function

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