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Nuclear localization of the caspase-3-cleaved form of p73 in anoikis
The transcription factor p73 is a homologue of p53 that can be expressed as pro- or anti-apoptotic isoforms. Unlike p53, p73 is rarely mutated or lost in cancers and it is found to replace defective p53 inducing apoptosis. Here, we investigated the p73 involvement in anoikis, a type of apoptosis cau...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914288/ https://www.ncbi.nlm.nih.gov/pubmed/26575022 http://dx.doi.org/10.18632/oncotarget.6329 |
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author | Alsafadi, Samar Tourpin, Sophie Bessoltane, Nadia Salomé-Desnoulez, Sophie Vassal, Gilles André, Fabrice Ahomadegbe, Jean-Charles |
author_facet | Alsafadi, Samar Tourpin, Sophie Bessoltane, Nadia Salomé-Desnoulez, Sophie Vassal, Gilles André, Fabrice Ahomadegbe, Jean-Charles |
author_sort | Alsafadi, Samar |
collection | PubMed |
description | The transcription factor p73 is a homologue of p53 that can be expressed as pro- or anti-apoptotic isoforms. Unlike p53, p73 is rarely mutated or lost in cancers and it is found to replace defective p53 inducing apoptosis. Here, we investigated the p73 involvement in anoikis, a type of apoptosis caused by inadequate cell-matrix interactions. Breast cancer cell lines with different p53 status were treated with doxorubicin (DOX) or docetaxel (DOC) and cells detached from the extracellular matrix were analyzed. We demonstrate for the first time that DOX-induced cell detachment is associated with p73 cleavage and caspase activation, independently of the p53 status. However, we did not detect p73 cleavage or caspase activation in detached cells under DOC treatment. Overexpressing the apoptotic isoform of p73 led to cell detachment associated with p73 cleavage and caspase activation. Interestingly, p73 cleaved forms localize to the nucleus during the late phase of cell death indicating an increase in the transcriptional activity. Our study suggests that the cleavage of p73 on specific sites may release its pro-apoptotic function and contribute to cell death. |
format | Online Article Text |
id | pubmed-4914288 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-49142882016-07-11 Nuclear localization of the caspase-3-cleaved form of p73 in anoikis Alsafadi, Samar Tourpin, Sophie Bessoltane, Nadia Salomé-Desnoulez, Sophie Vassal, Gilles André, Fabrice Ahomadegbe, Jean-Charles Oncotarget Research Paper The transcription factor p73 is a homologue of p53 that can be expressed as pro- or anti-apoptotic isoforms. Unlike p53, p73 is rarely mutated or lost in cancers and it is found to replace defective p53 inducing apoptosis. Here, we investigated the p73 involvement in anoikis, a type of apoptosis caused by inadequate cell-matrix interactions. Breast cancer cell lines with different p53 status were treated with doxorubicin (DOX) or docetaxel (DOC) and cells detached from the extracellular matrix were analyzed. We demonstrate for the first time that DOX-induced cell detachment is associated with p73 cleavage and caspase activation, independently of the p53 status. However, we did not detect p73 cleavage or caspase activation in detached cells under DOC treatment. Overexpressing the apoptotic isoform of p73 led to cell detachment associated with p73 cleavage and caspase activation. Interestingly, p73 cleaved forms localize to the nucleus during the late phase of cell death indicating an increase in the transcriptional activity. Our study suggests that the cleavage of p73 on specific sites may release its pro-apoptotic function and contribute to cell death. Impact Journals LLC 2015-10-26 /pmc/articles/PMC4914288/ /pubmed/26575022 http://dx.doi.org/10.18632/oncotarget.6329 Text en Copyright: © 2016 Alsafadi et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Alsafadi, Samar Tourpin, Sophie Bessoltane, Nadia Salomé-Desnoulez, Sophie Vassal, Gilles André, Fabrice Ahomadegbe, Jean-Charles Nuclear localization of the caspase-3-cleaved form of p73 in anoikis |
title | Nuclear localization of the caspase-3-cleaved form of p73 in anoikis |
title_full | Nuclear localization of the caspase-3-cleaved form of p73 in anoikis |
title_fullStr | Nuclear localization of the caspase-3-cleaved form of p73 in anoikis |
title_full_unstemmed | Nuclear localization of the caspase-3-cleaved form of p73 in anoikis |
title_short | Nuclear localization of the caspase-3-cleaved form of p73 in anoikis |
title_sort | nuclear localization of the caspase-3-cleaved form of p73 in anoikis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914288/ https://www.ncbi.nlm.nih.gov/pubmed/26575022 http://dx.doi.org/10.18632/oncotarget.6329 |
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