ER stress signaling in ARPE-19 cells after inhibition of protein kinase CK2 by CX-4945.

Abstract:

:Protein kinase CK2 is a critical factor for the survival of cells. It is overexpressed in many cancer cells and provides protection against apoptosis in these cells. Inhibition of CK2 kinase activity in various cancer cells leads to apoptosis, which makes CK2 an attractive target for cancer therapy. Little is, however, known about CK2 inhibition in non-cancerous cells. Using the human retinal pigment epithelial cell line ARPE-19, we analyzed the formation of reactive oxygen species (ROS) and the ER stress signaling pathway after CK2 inhibition with CX-4945. Following CK2 inhibition, we did not find any significant generation of ROS in neither ARPE-19 non-cancer cells nor in HCT116 cancer cells. We found an induction of the ER stress pathway including the activation of eIF2α and ATF4 in both cell types. This activation was sufficient for ARPE-19 cells to cope with the ER stress. Furthermore, in contrast to HCT116 cancer cells, there was no induction of the pro-apoptotic transcription factor CHOP and no induction of apoptosis in the ARPE-19 cells. Overexpression of CHOP, however, induced apoptosis in ARPE-19 cells indicating that this step in the ER stress pathway is abrogated in normal cells compared to cancer cell.

journal_name

Cell Signal

journal_title

Cellular signalling

authors

Intemann J,Saidu NE,Schwind L,Montenarh M

doi

10.1016/j.cellsig.2014.03.014

subject

Has Abstract

pub_date

2014-07-01 00:00:00

pages

1567-75

issue

7

eissn

0898-6568

issn

1873-3913

pii

S0898-6568(14)00116-8

journal_volume

26

pub_type

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