Skip to Main content Skip to Navigation
Journal articles

Regulation of the proapoptotic functions of prostate apoptosis response-4 (Par-4) by casein kinase 2 in prostate cancer cells

Abstract : The proapoptotic protein, prostate apoptosis response-4 (Par-4), acts as a tumor suppressor in prostate cancer cells. The serine/threonine kinase casein kinase 2 (CK2) has a well-reported role in prostate cancer resistance to apoptotic agents or anticancer drugs. However, the mechanistic understanding on how CK2 supports survival is far from complete. In this work, we demonstrate both in rat and humans that (i) Par-4 is a new substrate of the survival kinase CK2 and (ii) phosphorylation by CK2 impairs Par-4 proapoptotic functions. We also unravel different levels of CK2-dependent regulation of Par-4 between species. In rats, the phosphorylation by CK2 at the major site, S124, prevents caspase-mediated Par-4 cleavage (D123) and consequently impairs the proapoptotic function of Par-4. In humans, CK2 strongly impairs the apoptotic properties of Par-4, independently of the caspase-mediated cleavage of Par-4 (D131), by triggering the phosphorylation at residue S231. Furthermore, we show that human Par-4 residue S231 is highly phosphorylated in prostate cancer cells as compared with their normal counterparts. Finally, the sensitivity of prostate cancer cells to apoptosis by CK2 knockdown is significantly reversed by parallel knockdown of Par-4. Thus, Par-4 seems a critical target of CK2 that could be exploited for the development of new anticancer drugs.
Complete list of metadata

Cited literature [60 references]  Display  Hide  Download

https://hal.archives-ouvertes.fr/hal-02930263
Contributor : Mezger Valérie <>
Submitted on : Tuesday, September 22, 2020 - 11:30:34 AM
Last modification on : Tuesday, December 1, 2020 - 9:42:02 AM
Long-term archiving on: : Thursday, December 3, 2020 - 3:42:41 PM

File

cddis2013532.pdf
Publisher files allowed on an open archive

Licence


Distributed under a Creative Commons Attribution - NonCommercial - NoDerivatives 4.0 International License

Identifiers

Citation

Aurélie de Thonel, Adonis Hazoume, V. Kochin, K. Isoniemi, Gaetan Jego, et al.. Regulation of the proapoptotic functions of prostate apoptosis response-4 (Par-4) by casein kinase 2 in prostate cancer cells. Cell Death and Disease, Nature Publishing Group, 2014, 5 (1), pp.e1016-e1016. ⟨10.1038/cddis.2013.532⟩. ⟨hal-02930263⟩

Share

Metrics

Record views

110

Files downloads

178