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Δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells
The p53 isoform, Δ133p53β, is critical in promoting cancer. Here we report that Δ133p53β activity is regulated through an aggregation-dependent mechanism. Δ133p53β aggregates were observed in cancer cells and tumour biopsies. The Δ133p53β aggregation depends on association with interacting partners...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443592/ https://www.ncbi.nlm.nih.gov/pubmed/34526502 http://dx.doi.org/10.1038/s41467-021-25550-2 |
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author | Arsic, Nikola Slatter, Tania Gadea, Gilles Villain, Etienne Fournet, Aurelie Kazantseva, Marina Allemand, Frédéric Sibille, Nathalie Seveno, Martial de Rossi, Sylvain Mehta, Sunali Urbach, Serge Bourdon, Jean-Christophe Bernado, Pau Kajava, Andrey V. Braithwaite, Antony Roux, Pierre |
author_facet | Arsic, Nikola Slatter, Tania Gadea, Gilles Villain, Etienne Fournet, Aurelie Kazantseva, Marina Allemand, Frédéric Sibille, Nathalie Seveno, Martial de Rossi, Sylvain Mehta, Sunali Urbach, Serge Bourdon, Jean-Christophe Bernado, Pau Kajava, Andrey V. Braithwaite, Antony Roux, Pierre |
author_sort | Arsic, Nikola |
collection | PubMed |
description | The p53 isoform, Δ133p53β, is critical in promoting cancer. Here we report that Δ133p53β activity is regulated through an aggregation-dependent mechanism. Δ133p53β aggregates were observed in cancer cells and tumour biopsies. The Δ133p53β aggregation depends on association with interacting partners including p63 family members or the CCT chaperone complex. Depletion of the CCT complex promotes accumulation of Δ133p53β aggregates and loss of Δ133p53β dependent cancer cell invasion. In contrast, association with p63 family members recruits Δ133p53β from aggregates increasing its intracellular mobility. Our study reveals novel mechanisms of cancer progression for p53 isoforms which are regulated through sequestration in aggregates and recruitment upon association with specific partners like p63 isoforms or CCT chaperone complex, that critically influence cancer cell features like EMT, migration and invasion. |
format | Online Article Text |
id | pubmed-8443592 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-84435922021-10-04 Δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells Arsic, Nikola Slatter, Tania Gadea, Gilles Villain, Etienne Fournet, Aurelie Kazantseva, Marina Allemand, Frédéric Sibille, Nathalie Seveno, Martial de Rossi, Sylvain Mehta, Sunali Urbach, Serge Bourdon, Jean-Christophe Bernado, Pau Kajava, Andrey V. Braithwaite, Antony Roux, Pierre Nat Commun Article The p53 isoform, Δ133p53β, is critical in promoting cancer. Here we report that Δ133p53β activity is regulated through an aggregation-dependent mechanism. Δ133p53β aggregates were observed in cancer cells and tumour biopsies. The Δ133p53β aggregation depends on association with interacting partners including p63 family members or the CCT chaperone complex. Depletion of the CCT complex promotes accumulation of Δ133p53β aggregates and loss of Δ133p53β dependent cancer cell invasion. In contrast, association with p63 family members recruits Δ133p53β from aggregates increasing its intracellular mobility. Our study reveals novel mechanisms of cancer progression for p53 isoforms which are regulated through sequestration in aggregates and recruitment upon association with specific partners like p63 isoforms or CCT chaperone complex, that critically influence cancer cell features like EMT, migration and invasion. Nature Publishing Group UK 2021-09-15 /pmc/articles/PMC8443592/ /pubmed/34526502 http://dx.doi.org/10.1038/s41467-021-25550-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Arsic, Nikola Slatter, Tania Gadea, Gilles Villain, Etienne Fournet, Aurelie Kazantseva, Marina Allemand, Frédéric Sibille, Nathalie Seveno, Martial de Rossi, Sylvain Mehta, Sunali Urbach, Serge Bourdon, Jean-Christophe Bernado, Pau Kajava, Andrey V. Braithwaite, Antony Roux, Pierre Δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells |
title | Δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells |
title_full | Δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells |
title_fullStr | Δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells |
title_full_unstemmed | Δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells |
title_short | Δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells |
title_sort | δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443592/ https://www.ncbi.nlm.nih.gov/pubmed/34526502 http://dx.doi.org/10.1038/s41467-021-25550-2 |
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