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Post-translational regulation of the cleaved fragment of Par-4 in ovarian and endometrial cancer cells
We recently reported the caspase3-dependent cleavage of Par-4 resulting in the accumulation of a 25kDa cleaved-Par-4 (cl-Par-4) fragment and we investigated in the present study the mechanisms regulating this fragment using cl-Par-4-expressing stable clones derived from ovarian and endometrial cance...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095052/ https://www.ncbi.nlm.nih.gov/pubmed/27175591 http://dx.doi.org/10.18632/oncotarget.9235 |
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author | Brasseur, Kevin Fabi, François Adam, Pascal Parent, Sophie Lessard, Laurent Asselin, Eric |
author_facet | Brasseur, Kevin Fabi, François Adam, Pascal Parent, Sophie Lessard, Laurent Asselin, Eric |
author_sort | Brasseur, Kevin |
collection | PubMed |
description | We recently reported the caspase3-dependent cleavage of Par-4 resulting in the accumulation of a 25kDa cleaved-Par-4 (cl-Par-4) fragment and we investigated in the present study the mechanisms regulating this fragment using cl-Par-4-expressing stable clones derived from ovarian and endometrial cancer cell lines. Cl-Par-4 protein was weakly express in all stable clones despite constitutive expression. However, upon cisplatin treatment, cl-Par-4 levels increased up to 50-fold relative to baseline conditions. Treatment of stable clones with proteasome and translation inhibitors revealed that cisplatin exposure might in fact protect cl-Par-4 from proteasome-dependent degradation. PI3K and MAPK pathways were also implicated as evidenced by an increase of cl-Par-4 in the presence of PI3K inhibitors and a decrease using MAPK inhibitors. Finally using bioinformatics resources, we found diverse datasets showing similar results to those we observed with the proteasome and cl-Par-4 further supporting our data. These new findings add to the complex mechanisms regulating Par-4 expression and activity, and justify further studies addressing the biological significance of this phenomenon in gynaecological cancer cells. |
format | Online Article Text |
id | pubmed-5095052 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-50950522016-11-22 Post-translational regulation of the cleaved fragment of Par-4 in ovarian and endometrial cancer cells Brasseur, Kevin Fabi, François Adam, Pascal Parent, Sophie Lessard, Laurent Asselin, Eric Oncotarget Research Paper We recently reported the caspase3-dependent cleavage of Par-4 resulting in the accumulation of a 25kDa cleaved-Par-4 (cl-Par-4) fragment and we investigated in the present study the mechanisms regulating this fragment using cl-Par-4-expressing stable clones derived from ovarian and endometrial cancer cell lines. Cl-Par-4 protein was weakly express in all stable clones despite constitutive expression. However, upon cisplatin treatment, cl-Par-4 levels increased up to 50-fold relative to baseline conditions. Treatment of stable clones with proteasome and translation inhibitors revealed that cisplatin exposure might in fact protect cl-Par-4 from proteasome-dependent degradation. PI3K and MAPK pathways were also implicated as evidenced by an increase of cl-Par-4 in the presence of PI3K inhibitors and a decrease using MAPK inhibitors. Finally using bioinformatics resources, we found diverse datasets showing similar results to those we observed with the proteasome and cl-Par-4 further supporting our data. These new findings add to the complex mechanisms regulating Par-4 expression and activity, and justify further studies addressing the biological significance of this phenomenon in gynaecological cancer cells. Impact Journals LLC 2016-05-09 /pmc/articles/PMC5095052/ /pubmed/27175591 http://dx.doi.org/10.18632/oncotarget.9235 Text en Copyright: © 2016 Brasseur 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 Brasseur, Kevin Fabi, François Adam, Pascal Parent, Sophie Lessard, Laurent Asselin, Eric Post-translational regulation of the cleaved fragment of Par-4 in ovarian and endometrial cancer cells |
title | Post-translational regulation of the cleaved fragment of Par-4 in ovarian and endometrial cancer cells |
title_full | Post-translational regulation of the cleaved fragment of Par-4 in ovarian and endometrial cancer cells |
title_fullStr | Post-translational regulation of the cleaved fragment of Par-4 in ovarian and endometrial cancer cells |
title_full_unstemmed | Post-translational regulation of the cleaved fragment of Par-4 in ovarian and endometrial cancer cells |
title_short | Post-translational regulation of the cleaved fragment of Par-4 in ovarian and endometrial cancer cells |
title_sort | post-translational regulation of the cleaved fragment of par-4 in ovarian and endometrial cancer cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095052/ https://www.ncbi.nlm.nih.gov/pubmed/27175591 http://dx.doi.org/10.18632/oncotarget.9235 |
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