p53 is dispensable for the induction of apoptosis after inhibition of protein kinase CK2.
BACKGROUND
Protein kinase CK2 is a ubiquitously expressed heterotetramer consisting of two catalytic alpha/alpha' and two regulatory beta subunits. Expression of CK2 is highly elevated in tumor cells where it protects cells from apoptosis. A variety of different compounds were tested as inhibitors of protein kinase CK2 in order to find new therapy strategies. To analyze the role of p53 in the response to CK2 inhibition we used one of the most specific CK2 inhibitors available, TBB, in different prostate cancer cell lines.


METHODS
We treated prostate cancer cells with the CK2 inhibitor TBB and determined its effect on CK2 activity by an in vitro phosphorylation assay and its effect on viability by an MTT assay. Furthermore, we analyzed changes in the expression of p53 and PARP cleavage by Western Blot analysis.


RESULTS
Inhibition of CK2 by TBB led to a decrease in cell viability and apoptosis in two cell lines which express wild-type p53 whereas two other cell lines expressing mutant or no p53 failed to show signs of apoptosis. Moreover, cell lines expressing wild-type p53 showed an increase of the amount of p53 and of its transactivation efficiency. However, down-regulation of p53 by RNAi showed that p53 is not necessary for the induction of apoptosis.


CONCLUSIONS
Wild-type p53 is not necessary for the induction of apoptosis by TBB in prostate cancer cells.
Schneider
Carolin C
CC
Medizinische Biochemie und Molekularbiologie, Universität des Saarlandes, Homburg, Germany.
Hessenauer
Andrea
A
Montenarh
Mathias
M
Götz
Claudia
C
D017209:Apoptosis / Q000187:drug effects*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
C405354:4,5,6,7-tetrabromobenzotriazole; D004791:Enzyme Inhibitors; D014230:Triazoles; D016159:Tumor Suppressor Protein p53; D047390:Casein Kinase II