Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Brasseur, Kevin, Fabi, François, Adam, Pascal, Parent, Sophie, Lessard, Laurent, Asselin, Eric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
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
_version_ 1782465225687040000
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
work_keys_str_mv AT brasseurkevin posttranslationalregulationofthecleavedfragmentofpar4inovarianandendometrialcancercells
AT fabifrancois posttranslationalregulationofthecleavedfragmentofpar4inovarianandendometrialcancercells
AT adampascal posttranslationalregulationofthecleavedfragmentofpar4inovarianandendometrialcancercells
AT parentsophie posttranslationalregulationofthecleavedfragmentofpar4inovarianandendometrialcancercells
AT lessardlaurent posttranslationalregulationofthecleavedfragmentofpar4inovarianandendometrialcancercells
AT asselineric posttranslationalregulationofthecleavedfragmentofpar4inovarianandendometrialcancercells