CASEIN-KINASE-2 INHIBITS THE RENATURATION OF COMPLEMENTARY-DNA STRANDS MEDIATED BY P53 PROTEIN

Considerable effort is currently being devoted to understand the funct ions of protein p53, a major regulator of cell proliferation. The prot ein p53 has been reported to catalyse the annealing of complementary D NA or RNA strands. We report that this activity is inhibited in the pr esence of the serine/threonine protein kinase CK2. It is shown that th is inhibition can be explained by the occurrence of a high-affinity mo lecular association between p53 and CK2. The molecular complex involve s an interaction between the C-terminal domain of p53 and the beta sub unit of the oligomeric kinase. Accordingly, the isolated a subunit of the kinase was without effect. In addition, after phosphorylation by C K2, phosphorylated p53 lost its DNA annealing activity. Because the C- terminal domain of p53 is both involved in the association with CK2 an d phosphorylated by it, our results suggest that either protein-protei n interaction or phosphorylation of this domain might control the base pairing of complementary sequences promoted by p53 in processes relat ed to DNA replication and repair.