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Self-association of the APC tumor suppressor is required for the assembly, stability, and activity of the Wnt signaling destruction complex

The tumor suppressor adenomatous polyposis coli (APC) is an essential negative regulator of Wnt signaling through its activity in the destruction complex with Axin, GSK3β, and CK1 that targets β-catenin/Armadillo (β-cat/Arm) for proteosomal degradation. The destruction complex forms macromolecular p...

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Autores principales: Kunttas-Tatli, Ezgi, Roberts, David M., McCartney, Brooke M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214788/
https://www.ncbi.nlm.nih.gov/pubmed/25208568
http://dx.doi.org/10.1091/mbc.E14-04-0885
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author Kunttas-Tatli, Ezgi
Roberts, David M.
McCartney, Brooke M.
author_facet Kunttas-Tatli, Ezgi
Roberts, David M.
McCartney, Brooke M.
author_sort Kunttas-Tatli, Ezgi
collection PubMed
description The tumor suppressor adenomatous polyposis coli (APC) is an essential negative regulator of Wnt signaling through its activity in the destruction complex with Axin, GSK3β, and CK1 that targets β-catenin/Armadillo (β-cat/Arm) for proteosomal degradation. The destruction complex forms macromolecular particles we termed the destructosome. Whereas APC functions in the complex through its ability to bind both β-cat and Axin, we hypothesize that APC proteins play an additional role in destructosome assembly through self-association. Here we show that a novel N-terminal coil, the APC self-association domain (ASAD), found in vertebrate and invertebrate APCs, directly mediates self-association of Drosophila APC2 and plays an essential role in the assembly and stability of the destructosome that regulates β-cat degradation in Drosophila and human cells. Consistent with this, removal of the ASAD from the Drosophila embryo results in β-cat/Arm accumulation and aberrant Wnt pathway activation. These results suggest that APC proteins are required not only for the activity of the destructosome, but also for the assembly and stability of this macromolecular machine.
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spelling pubmed-42147882015-01-16 Self-association of the APC tumor suppressor is required for the assembly, stability, and activity of the Wnt signaling destruction complex Kunttas-Tatli, Ezgi Roberts, David M. McCartney, Brooke M. Mol Biol Cell Articles The tumor suppressor adenomatous polyposis coli (APC) is an essential negative regulator of Wnt signaling through its activity in the destruction complex with Axin, GSK3β, and CK1 that targets β-catenin/Armadillo (β-cat/Arm) for proteosomal degradation. The destruction complex forms macromolecular particles we termed the destructosome. Whereas APC functions in the complex through its ability to bind both β-cat and Axin, we hypothesize that APC proteins play an additional role in destructosome assembly through self-association. Here we show that a novel N-terminal coil, the APC self-association domain (ASAD), found in vertebrate and invertebrate APCs, directly mediates self-association of Drosophila APC2 and plays an essential role in the assembly and stability of the destructosome that regulates β-cat degradation in Drosophila and human cells. Consistent with this, removal of the ASAD from the Drosophila embryo results in β-cat/Arm accumulation and aberrant Wnt pathway activation. These results suggest that APC proteins are required not only for the activity of the destructosome, but also for the assembly and stability of this macromolecular machine. The American Society for Cell Biology 2014-11-01 /pmc/articles/PMC4214788/ /pubmed/25208568 http://dx.doi.org/10.1091/mbc.E14-04-0885 Text en © 2014 Kunttas-Tatli et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Kunttas-Tatli, Ezgi
Roberts, David M.
McCartney, Brooke M.
Self-association of the APC tumor suppressor is required for the assembly, stability, and activity of the Wnt signaling destruction complex
title Self-association of the APC tumor suppressor is required for the assembly, stability, and activity of the Wnt signaling destruction complex
title_full Self-association of the APC tumor suppressor is required for the assembly, stability, and activity of the Wnt signaling destruction complex
title_fullStr Self-association of the APC tumor suppressor is required for the assembly, stability, and activity of the Wnt signaling destruction complex
title_full_unstemmed Self-association of the APC tumor suppressor is required for the assembly, stability, and activity of the Wnt signaling destruction complex
title_short Self-association of the APC tumor suppressor is required for the assembly, stability, and activity of the Wnt signaling destruction complex
title_sort self-association of the apc tumor suppressor is required for the assembly, stability, and activity of the wnt signaling destruction complex
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214788/
https://www.ncbi.nlm.nih.gov/pubmed/25208568
http://dx.doi.org/10.1091/mbc.E14-04-0885
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