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

Oncogene. 2005 Mar 17;24(12):2050-8. doi: 10.1038/sj.onc.1208397.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma
  • Apigenin / pharmacology
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins
  • Casein Kinase II / metabolism*
  • Cell Death / drug effects
  • Cell Death / physiology*
  • Cell Line, Tumor
  • Colonic Neoplasms
  • Death Domain Receptor Signaling Adaptor Proteins
  • Enzyme Inhibitors / pharmacology
  • Genetic Vectors
  • Humans
  • Indoles / pharmacology
  • Kinetics
  • Maleimides / pharmacology
  • Membrane Glycoproteins / metabolism*
  • Receptors, Tumor Necrosis Factor / physiology*
  • Recombinant Proteins / metabolism
  • TNF-Related Apoptosis-Inducing Ligand
  • Transfection
  • Tumor Necrosis Factor-alpha / metabolism*


  • Apoptosis Regulatory Proteins
  • Death Domain Receptor Signaling Adaptor Proteins
  • Enzyme Inhibitors
  • Indoles
  • Maleimides
  • Membrane Glycoproteins
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha
  • Apigenin
  • Casein Kinase II
  • bisindolylmaleimide