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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2005-3-17
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Apigenin,
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Casein Kinase II,
http://linkedlifedata.com/resource/pubmed/chemical/Death Domain Receptor Signaling...,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Maleimides,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TNF-Related Apoptosis-Inducing...,
http://linkedlifedata.com/resource/pubmed/chemical/TNFSF10 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/bisindolylmaleimide
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0950-9232
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
17
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pubmed:volume |
24
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2050-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15688023-Adenocarcinoma,
pubmed-meshheading:15688023-Apigenin,
pubmed-meshheading:15688023-Apoptosis,
pubmed-meshheading:15688023-Apoptosis Regulatory Proteins,
pubmed-meshheading:15688023-Casein Kinase II,
pubmed-meshheading:15688023-Cell Death,
pubmed-meshheading:15688023-Cell Line, Tumor,
pubmed-meshheading:15688023-Colonic Neoplasms,
pubmed-meshheading:15688023-Death Domain Receptor Signaling Adaptor Proteins,
pubmed-meshheading:15688023-Enzyme Inhibitors,
pubmed-meshheading:15688023-Genetic Vectors,
pubmed-meshheading:15688023-Humans,
pubmed-meshheading:15688023-Indoles,
pubmed-meshheading:15688023-Kinetics,
pubmed-meshheading:15688023-Maleimides,
pubmed-meshheading:15688023-Membrane Glycoproteins,
pubmed-meshheading:15688023-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:15688023-Recombinant Proteins,
pubmed-meshheading:15688023-TNF-Related Apoptosis-Inducing Ligand,
pubmed-meshheading:15688023-Transfection,
pubmed-meshheading:15688023-Tumor Necrosis Factor-alpha
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pubmed:year |
2005
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pubmed:articleTitle |
Casein kinase II (CK2) enhances death-inducing signaling complex (DISC) activity in TRAIL-induced apoptosis in human colon carcinoma cell lines.
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pubmed:affiliation |
Division of Molecular Therapeutics, Department of Hematology-Oncology, St Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA. kamel.izeradjene@stjude.org
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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