Downregulation of the cdc2/Cyclin B Protein Kinase Activity by Binding of p53 to p34 cdc2

We previously found that p53 binds to the catalytic subunit of the p34 cdc2 /cyclin B1–kinase. In the present study we analyzed the functional consequences of this interaction. Binding of wild-type p53 to p34 cdc2 /cyclin B1 results in a significant decrease of its histone H1 kinase activity. Binding of p53 to the kinase is a prerequisite for the inhibition because a mutant p53 which lacks the binding region fails to influence the enzymatic activity. Furthermore, by using C-terminal fragments of p53 it became obvious that also some other structural elements in the N-terminal region are necessary for the inhibitory effect. Our present study provides evidence that p53 might regulate cell-cycle checkpoints not only on the transcriptional level but also by binding to the cell-cycle regulating kinase p34 cdc2.