Nuclear-cytoplasmic shuttling of Axin regulates subcellular localization of β-catenin Journal Article
| Authors: | Cong, F.; Varmus, H. |
| Article Title: | Nuclear-cytoplasmic shuttling of Axin regulates subcellular localization of β-catenin |
| Abstract: | Wnt signaling regulates many aspects of development by increasing the signaling activity of β-catenin. Axin is a negative regulator of the Wnt signaling pathway, and it is responsible for the formation of the β-catenin degradation complex. Genetic studies with Drosophila suggest that Axin promotes cytoplasmic localization of β-catenin independent of Axin's known role of enhancing degradation of β-catenin. Here, we show that Axin is a nuclear-cytoplasmic shuttling protein. Nuclear export of Axin depends on the chromosome maintenance region 1 nuclear receptor; treatment with the chromosome maintenance region 1 inhibitor leptomycin B induces nuclear accumulation of ectopically expressed or endogenous Axin. Functional nuclear localization and nuclear export signals have been mapped within Axin. Significantly, overexpression of an Axin fragment shifts coexpressed stabilized β-catenin to the cytoplasm, and this effect requires shuttling of Axin between the cytoplasm and the nucleus. Our results suggest that Axin functions as a molecular chaperone for β-catenin and that nuclear-cytoplasmic shuttling of Axin regulates the nuclear-cytoplasmic distribution of β-catenin. |
| Keywords: | signal transduction; controlled study; protein expression; unclassified drug; human cell; nonhuman; protein function; protein localization; animal cell; chromosome; animals; embryo; protein degradation; protein protein interaction; cell line; drosophila; transfection; cercopithecus aethiops; cos cells; animalia; protein transport; cytoplasm; trans-activators; cell nucleus; cell transport; cell nucleus receptor; beta catenin; repressor proteins; wnt protein; axin; cytoskeletal proteins; receptors, cytoplasmic and nuclear; leptomycin b; fatty acids, unsaturated; humans; human; priority journal; article; chromosome maintenance region 1 nuclear receptor |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 101 |
| Issue: | 9 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2004-03-02 |
| Start Page: | 2882 |
| End Page: | 2887 |
| Language: | English |
| DOI: | 10.1073/pnas.0307344101 |
| PROVIDER: | scopus |
| PUBMED: | 14981260 |
| PMCID: | PMC365714 |
| DOI/URL: | |
| Notes: | Proc. Natl. Acad. Sci. U. S. A. -- Cited By (since 1996):103 -- Export Date: 16 June 2014 -- CODEN: PNASA -- Source: Scopus |
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