p53 regulates a G2 checkpoint through cyclin B1

p53 regulates a G₂ checkpoint through cyclin B1

^*Hamilton Regional Cancer Center, 699 Concession Street, Hamilton, Ontario, Canada L8V 5C2; ^†Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9; ^‡Department of Molecular Genetics, Glaxo Research Institute, Research Triangle Park, NC 27709; and ^§Department of Pathology, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8B 3Z5

Edited by Arthur B. Pardee, Dana–Farber Cancer Institute, Boston, MA, and approved December 21, 1998 (received for review October 13, 1998)

Abstract

The p53 tumor suppressor controls multiple cell cycle checkpoints regulating the mammalian response to DNA damage. To identify the mechanism by which p53 regulates G₂, we have derived a human ovarian cell that undergoes p53-dependent G₂ arrest at 32°C. We have found that p53 prevents G₂/M transition by decreasing intracellular levels of cyclin B1 protein and attenuating the activity of the cyclin B1 promoter. Cyclin B1 is the regulatory subunit of the cdc2 kinase and is a protein required for mitotic initiation. The ability of p53 to control mitotic initiation by regulating intracellular cyclin B1 levels suggests that the cyclin B-dependent G₂ checkpoint has a role in preventing neoplastic transformation.

Footnotes

↵ ¶ To whom reprint requests should be addressed at the ∗ address. e-mail: jonathan_lee{at}hrcc.on.ca.
This paper was submitted directly (Track II) to the Proceedings Office.
ABBREVIATIONS:

RT,

room temperature;

CAT,

chloramphenicol acetyltransferase