A Potential Role of Nuclear Matrix-associated Protein Kinase CK2 in Protection against Drug-induced Apoptosis in Cancer Cells

Alan T. Davis,Jeffrey E. Green,Khalil Ahmed,Huamin Wang,Shihui Yu,Chuanhai Guo

doi:10.1074/jbc.m004862200

Abstract

Protein kinase CK2 (CK2) has long been implicated in the regulation of cell growth and proliferation. Its activity is generally elevated in rapidly proliferating tissues, and nuclear matrix (NM) is an important subnuclear locale of its functional signaling. In the prostate, nuclear CK2 is rapidly lost commensurate with induction of receptor-mediated apoptosis after growth stimulus withdrawal. By contrast, chemical-induced apoptosis in prostate cancer and other cells (by etoposide and diethylstilbestrol) evokes an enhancement in CK2 associated with the NM that appears to be because of translocation of CK2 from the cytoplasmic to the nuclear compartment. This shuttling of CK2 to the NM may reflect a protective response to chemical-mediated apoptosis. Supporting evidence for this was obtained by employing cells that were transiently transfected with various expression plasmids of CK2 (thereby expressing additional CK2) prior to treatment with etoposide or diethylstilbestrol. Cells transfected with the CK2alpha or CK2alphabeta showed significant resistance to chemical-mediated apoptosis commensurate with the corresponding elevation in CK2 in the NM. Transfection with CK2beta did not demonstrate this effect. These results suggest, for the first time, that besides the commonly appreciated function of CK2 in cell growth, it may also have a role in protecting cells against apoptosis.

Highlights

Protein kinase CK2 (CK2) has long been implicated in the regulation of cell growth and proliferation
This paper is available on line at http://www.jbc.org employing receptor-mediated apoptosis in the prostate epithelial cells has shown a distinct response of nuclear matrix (NM)-associated CK2 such that a rapid loss of CK2 from the NM compartment temporally precedes the appearance of apoptosis [1, 9, 11, 14, 15, 24]
In the present paper we report that etoposide and diethylstilbestrol (DES), employed as models for chemical-induced apoptosis, demonstrate a distinctly different response of CK2 in the NM when compared with the previous observations on receptor-mediated induction of apoptosis

Summary

Introduction

Protein kinase CK2 (CK2) has long been implicated in the regulation of cell growth and proliferation. This paper is available on line at http://www.jbc.org employing receptor-mediated apoptosis in the prostate epithelial cells has shown a distinct response of NM-associated CK2 such that a rapid loss of CK2 from the NM compartment temporally precedes the appearance of apoptosis [1, 9, 11, 14, 15, 24]. No such studies have been reported on the response of the CK2 signal in relation to chemical-mediated apoptosis in cancer cells. Considering the distinct nature of the receptor-mediated and chemical-mediated apoptosis, we decided to examine the nature of CK2 dynamics in the NM under the latter conditions

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Conclusion