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Impact of protein kinase CK2 on inhibitor of apoptosis proteins in prostate cancer cells

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Abstract

We have previously demonstrated that protein kinase CK2 is a potent suppressor of apoptosis in cells subjected to diverse mediators of apoptosis. The process of apoptosis involves a complex series of molecules localized in various cellular compartments. Among the various proteins that modulate apoptotic activity are inhibitors of apoptosis proteins (IAPs) which are elevated in cancers and have been proposed to block caspase activity. We have examined the impact of CK2 signal on these proteins in prostate cancer cells. Cellular IAPs demonstrate distinct localization and responsiveness to altered CK2 expression or activity in the cytoplasmic and nuclear matrix fractions. Modulation of cellular CK2 by various approaches impacts on cellular IAPs such that inhibition or downregulation of CK2 results in reduction in these proteins. Further, IAPs are also reduced when cells are treated with sub-optimal concentrations of chemical inhibitors of CK2 combined with low or sub-optimal levels of apoptosis-inducing agents (such as etoposide) suggesting that downregulation of CK2 sensitizes cells to induction of apoptosis which may be related to attenuation of IAPs. Decreased IAP protein levels in response to apoptotic agents such as TNFα or TRAIL were potently blocked upon forced overexpression of CK2 in cells. Together, our results suggest that one of the modes of CK2-mediated modulation of apoptotic activity is via its impact on cellular IAPs.

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Abbreviations

CK2:

Acronym for the former name casein kinase II

CK2α:

CK2 catalytic subunit α

CK2β:

CK2 regulatory subunit β

IAPs:

Inhibitor of apoptosis proteins such as cIAP1, cIAP2, XIAP, survivin

TBB:

4,5,6,7-Tetrabromobenzotriazole

MNA:

1,8-Dihydroxy-4-nitro-anthracene-9,10-dione

TRAIL:

Tumor necrosis factor-related apoptosis inducing ligand

TNFα:

Tumor necrosis factor α

FBS:

Fetal bovine serum

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Acknowledgments

This work is supported in part by funds from USPHS Research Grant CA-15062 awarded by the National Cancer Institute, Department of Health and Human Services, and in part by the Medical Research Fund of the U.S. Department of Veterans Affairs. We deeply appreciate the critical comments of Dr. J. Trembley during preparation of the manuscript.

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Author notes

  1. Kashif A. Ahmad

    Present address: Northwestern Health Sciences University, Bloomington, MN, USA

Authors and Affiliations

  1. Cellular and Molecular Biochemistry Research Laboratory (151), Minneapolis Veterans Affairs Medical Center, University of Minnesota, One Veterans Drive, Minneapolis, MN, 55417, USA

    Guixia Wang, Kashif A. Ahmad, Nathan H. Harris & Khalil Ahmed

  2. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, 55417, USA

    Guixia Wang, Kashif A. Ahmad, Nathan H. Harris & Khalil Ahmed

  3. Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55417, USA

    Guixia Wang, Kashif A. Ahmad, Nathan H. Harris & Khalil Ahmed

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  1. Guixia Wang
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Correspondence to Khalil Ahmed.

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Wang, G., Ahmad, K.A., Harris, N.H. et al. Impact of protein kinase CK2 on inhibitor of apoptosis proteins in prostate cancer cells. Mol Cell Biochem 316, 91–97 (2008). https://doi.org/10.1007/s11010-008-9810-9

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  • DOI: https://doi.org/10.1007/s11010-008-9810-9

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