Wild-type p53 inhibits protein kinase CK2 activity.
The growth suppressor protein p53 and the protein kinase CK2 are both implicated in cellular growth regulation. We previously found that p53 binds to protein kinase CK2 via its regulatory beta-subunit. In the present study, we analyzed the consequences of the binding of p53 to CK2 for the enzymatic activity of CK2 in vitro and in vivo. We found that the carboxy-terminus of p53 which is a potent transforming agent stimulated CK2 activity whereas full length wild-type p53 which is a growth suppressor inhibited the activity of protein kinase CK2. Inhibition of protein kinase CK2 by p53 was dose-dependent and was seen for various CK2 substrates. Experiments with heat-denatured p53 and the conformational mutant p53(R175H) revealed that an intact conformation of p53 seemed to be necessary. Transfection of wild-type and of mutant p53 into p53-/- cells showed that the inhibition of p53 on CK2 activity was also detectable in intact cells and specific for wild-type p53 indicating that the growth suppressing function of p53 might at least be partially achieved by down-regulation of protein kinase CK2.
Schuster
N
N
Medical Biochemistry and Molecular Biology, University of the Saarland, D-66424 Homburg, Germany.
Götz
C
C
Faust
M
M
Schneider
E
E
Prowald
A
A
Jungbluth
A
A
Montenarh
M
M
D000595:Amino Acid Sequence; D047390:Casein Kinase II; D002460:Cell Line; D006801:Humans; D009687:Nuclear Proteins; D010766:Phosphorylation; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013379:Substrate Specificity; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000502:physiology*
D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases