Wild-type p53 inhibits protein kinase CK2 activity

The growth suppressor protein p53 and the protein kinase CK2 are both impli cated in cellular growth regulation. We previously found that p53 binds to protein kinase CK2 via its regulatory beta -subunit. In the prevent 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 o f p53 which is a potent transforming agent stimulated CK2 activity whereas full length wild-type p53 which is a growth suppressor inhibited the activi ty of protein kinase CK2. Inhibition of protein kinase CK2 by p53 was dose- dependent and was seen for various CK2 substrates. Experiments with heat-de natured p53 and the conformational mutant P53(R175H) revealed that an intac t 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 p5 3 indicating that the growth suppressing function of p53 might at least be partially achieved by down-regulation of protein kinase CK2. (C) 2001 Wiley -Liss, Inc.