Open AccessPost-translational regulation of the cleaved fragment of Par-4 in ovarian and endometrial cancer cells
Author(s) -
Kevin Brasseur,
François Fabi,
Pascal Adam,
Stefan Parent,
Laurent Lessard,
Éric Asselin
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.9235
Subject(s) - proteasome , ovarian cancer , cisplatin , endometrial cancer , mapk/erk pathway , cancer research , translation (biology) , pi3k/akt/mtor pathway , ubiquitin , biology , chemistry , cancer , apoptosis , microbiology and biotechnology , messenger rna , signal transduction , biochemistry , gene , genetics , chemotherapy
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.