Casein kinase II (CK2) enhances death-inducing signaling complex (DISC) activity in TRAIL-induced apoptosis in human colon carcinoma cell lines
| Autor: | Janet A. Houghton, Kamel Izeradjene, Leslie Douglas, Addison Delaney |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Death Domain Receptor Signaling Adaptor Proteins
Cancer Research medicine.medical_specialty Indoles animal structures Genetic Vectors Apoptosis Adenocarcinoma Biology Transfection medicine.disease_cause Receptors Tumor Necrosis Factor Maleimides TNF-Related Apoptosis-Inducing Ligand Cell Line Tumor Internal medicine Casein Genetics medicine Humans Apigenin Enzyme Inhibitors Casein Kinase II Molecular Biology chemistry.chemical_classification Membrane Glycoproteins Cell Death Tumor Necrosis Factor-alpha Kinase Recombinant Proteins Kinetics Enzyme Endocrinology chemistry Cell culture Colonic Neoplasms Death-inducing signaling complex Cancer research Casein kinase 2 Apoptosis Regulatory Proteins Carcinogenesis |
| Zdroj: | Oncogene. 24:2050-2058 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1208397 |
| Popis: | 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-kappaB. 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 CK2alpha in HT29 cells following transfection of CK2alpha 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. |
| Databáze: | OpenAIRE |
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