Validation of protein kinase CK2 as oncological target.
Protein kinase CK2 is a highly conserved enzyme composed of two catalytic subunits alpha and/or alpha' and two regulatory subunits beta whose activity is elevated in diverse tumour types as well as in highly proliferating tissues. Several results suggest that the overexpression of either CK2 catalytic subunits or the CK2 holoenzyme contributes to cellular transformation. In a similar vein, experiments performed compromising the intracellular expression of CK2 has led to somehow contradictory results with respect to the ability of this enzyme to control survival and apoptosis. To better elucidate the role of CK2 in programmed cell death, we have depleted cells of CK2 catalytic subunits by the application of antisense oligodeoxynucleotides and siRNAs techniques, respectively. Our results indicate that protein kinase CK2 is characterized by an extremely high stability that might be due to its association with other intracellular proteins, enhanced half-life or lower vulnerability towards proteolytic degradation. In addition, we show that despite the effectiveness of the methods applied in lowering CK2 kinase activity in all cells investigated, CK2 might not by itself be sufficient to trigger enhanced drug-induced apoptosis in cells.
Seeber
S
S
Roche Diagnostics GmbH, Pharma Research Penzberg, Nonnenwald 2, D-82377 Penzberg, Germany.
Issinger
O G
OG
Holm
T
T
Kristensen
L P
LP
Guerra
B
B
D017209:Apoptosis / Q000187:drug effects; D047390:Casein Kinase II / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain; D002471:Cell Transformation, Neoplastic; D005434:Flow Cytometry; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D009369:Neoplasms / Q000201:enzymology*; D015739:Nocodazole / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D034741:RNA, Small Interfering / Q000494:pharmacology; D015203:Reproducibility of Results
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D047390:Casein Kinase II; D015739:Nocodazole