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Casein kinase II (CK2) enhances death-inducing signaling complex (DISC) activity in TRAIL-induced apoptosis in human colon carcinoma cell lines

Oncogene volume 24, pages 2050–2058 (2005)Cite this article

Abstract

Protein kinase casein kinase II (CK2) is increased in response to diverse growth stimuli, as well as being elevated in many human cancers examined. We have demonstrated that CK2 is a key survival factor that protects human colon carcinoma cells from TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. We determined that inhibition of CK2 phosphorylation events by DRB (5,6-dichlorobenzimidazole) resulted in dramatic sensitization of tumor cells to TRAIL-induced apoptosis, in the absence of effects in normal cells. Sensitization was caspase dependent, and independent of regulation via NF-κB. Further, inhibition of phosphorylation by CK2 did not modify the expression level of antiapoptotic proteins. Analysis of TRAIL-induced death-inducing signaling complex (DISC) formation demonstrated enhanced formation of the DISC, enhanced cleavage of caspase-8 and cleavage of Bid in the presence of DRB, thereby facilitating the release of proapoptotic factors from the mitochondria with subsequent downregulation of the expression of XIAP and c-IAP1. Further, silencing of CK2α in HT29 cells following transfection of CK2α shRNA abrogated CK2 kinase activity while simultaneously increasing TRAIL sensitivity. These findings demonstrate that CK2 plays a critical antiapoptotic role by conferring resistance to TRAIL at the level of the DISC.

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Abbreviations

CK2:

casein kinase II

TRAIL:

TNF-related apoptosis-inducing ligand

GFP:

green fluorescence protein

DISC:

death-inducing signaling complex

DRB:

5,6-dichlorobenzimidazole

IAP:

inhibitor of apoptosis protein

shRNA:

short hairpin RNA

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Acknowledgements

This research was supported by NIH Awards CA 32613, Cancer Center Support (CORE) Grant CA 21765 and by the American Lebanese Syrian Associated Charities.

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  1. Division of Molecular Therapeutics, Department of Hematology-Oncology, St Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN, 38105, USA

    Kamel Izeradjene, Leslie Douglas, Addison Delaney & Janet A Houghton

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  1. Kamel Izeradjene
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  2. Leslie Douglas
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Correspondence to Kamel Izeradjene.

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Izeradjene, K., Douglas, L., Delaney, A. et al. Casein kinase II (CK2) enhances death-inducing signaling complex (DISC) activity in TRAIL-induced apoptosis in human colon carcinoma cell lines. Oncogene 24, 2050–2058 (2005). https://doi.org/10.1038/sj.onc.1208397

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