Impact of protein kinase CK2 on inhibitor of apoptosis proteins in prostate cancer cells.
We have previously demonstrated that protein kinase CK2 is a potent suppressor of apoptosis in cells subjected to diverse mediators of apoptosis. The process of apoptosis involves a complex series of molecules localized in various cellular compartments. Among the various proteins that modulate apoptotic activity are inhibitors of apoptosis proteins (IAPs) which are elevated in cancers and have been proposed to block caspase activity. We have examined the impact of CK2 signal on these proteins in prostate cancer cells. Cellular IAPs demonstrate distinct localization and responsiveness to altered CK2 expression or activity in the cytoplasmic and nuclear matrix fractions. Modulation of cellular CK2 by various approaches impacts on cellular IAPs such that inhibition or downregulation of CK2 results in reduction in these proteins. Further, IAPs are also reduced when cells are treated with sub-optimal concentrations of chemical inhibitors of CK2 combined with low or sub-optimal levels of apoptosis-inducing agents (such as etoposide) suggesting that downregulation of CK2 sensitizes cells to induction of apoptosis which may be related to attenuation of IAPs. Decreased IAP protein levels in response to apoptotic agents such as TNFalpha or TRAIL were potently blocked upon forced overexpression of CK2 in cells. Together, our results suggest that one of the modes of CK2-mediated modulation of apoptotic activity is via its impact on cellular IAPs.
Cellular and Molecular Biochemistry Research Laboratory (151), Minneapolis Veterans Affairs Medical Center, University of Minnesota, One Veterans Drive, Minneapolis, MN 55417, USA.
Guixia
G
Wang
Kashif A
KA
Ahmad
Nathan H
NH
Harris
Khalil
K
Ahmed
D047310:Apigenin / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013347:Subcellular Fractions / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology
C405354:4,5,6,7-tetrabromobenzotriazole; D051017:Apoptosis Regulatory Proteins; D047428:Protein Kinase Inhibitors; D014230:Triazoles; D047310:Apigenin; D047390:Casein Kinase II; D020169:Caspases