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 consequ ences of this interaction. Binding of wild-type p53 to p34(cdc2)/cyclin B1 results in a significant decrease of its histone H1 kinase activity. Bindin g of p53 to the kinase is a prerequisite for the inhibition because a mutan t p53 which lacks the binding region fails to influence the enzymatic activ ity. Furthermore, by using C-terminal fragments of p53 it became obvious th at also some other structural elements in the N-terminal region are necessa ry 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) (C) 2001 Academic Press.