Modulation of death receptor-mediated apoptosis by CK2.
Protein kinase CK2 has long been known to be involved in cell growth and proliferation. Recent work has also implicated its role in the suppression of apoptosis. We originally documented that removal of survival or growth stimuli resulted in rapid loss of CK2 from the nuclear matrix and chromatin which preceded induction of apoptosis. Further, we demonstrated that overexpression of CK2 in cells promotes suppression of drug-mediated apoptosis. In the present work, we have extended these observations to demonstrate that CK2 can influence apoptosis mediated via the death receptors. Overexpression of CK2 resulted in suppression of apoptosis mediated by TNF-alpha, TRAIL, and Fas-L in cells responsive to these ligands, whereas downregulation of CK2 resulted in augmentation of apoptosis mediated by these ligands. To our knowledge, this is the first report to show that receptor-mediated apoptosis can be modulated by changes in CK2 in prostate cancer cells. Based on our previous observations together with the evidence presented here, we propose that CK2 has an impact on the process of apoptosis mediated by diverse type of mechanisms thus playing a global role in regulation of apoptotic activity in cells.
Wang
Guixia
G
Cellular and Molecular Biochemistry Research Laboratory (151), Minneapolis Veterans Affairs Medical Center, MN 55417, USA.
Ahmad
Kashif A
KA
Ahmed
Khalil
K
D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D047390:Casein Kinase II / Q000502:physiology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000502:physiology; D002470:Cell Survival; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology; D015530:Nuclear Matrix / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D048069:Tumor Necrosis Factors / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; D047390:Casein Kinase II