p53 regulates a G(2) checkpoint through cyclin B1

The p53 tumor suppressor controls multiple cell cycle checkpoints regulatin g the mammalian response to DNA damage. To identify the mechanism by which p53 regulates G(2), we have derived a human ovarian cell that undergoes p53 -dependent G(2) arrest at 32 degrees C. We have found that p53 prevents G(2 )/M transition by decreasing intracellular levels of cyclin B1 protein and attenuating the activity of the cyclin B1 promoter. Cyclin B1 is the regula tory subunit of the cdc2 kinase and is a protein required for mitotic initi ation. The ability of p53 to control mitotic initiation by regulating intra cellular cyclin B1 levels suggests that the cyclin B-dependent G(2) checkpo int has a role in preventing neoplastic transformation.