Research Papers:
Posttranslational regulation of the cleaved fragment of Par4 in ovarian and endometrial cancer cells
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Kevin Brasseur1, François Fabi1, Pascal Adam1, Sophie Parent1, Laurent Lessard1, Eric Asselin1
1Research Group in Cellular Signaling, Department of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, Québec G9A 5H7, Canada
Correspondence to:
Eric Asselin, email: [email protected]
Keywords: Par-4, PI3K, MAPK, proteasome, gynaecological cancers
Received: December 17, 2015 Accepted: April 24, 2016 Published: May 9, 2016
ABSTRACT
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.