p53 regulates a G2 checkpoint through cyclin B1

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 96; no. 5; pp. 2147 - 2152
• Main Authors: Innocente, S A, Abrahamson, J L, Cogswell, J P, Lee, J M
• Format: Journal Article
• Language: English
• Published: United States National Acad Sciences 02.03.1999; National Academy of Sciences; The National Academy of Sciences
• Subjects: Animals; Biological Sciences; CDC2 Protein Kinase - metabolism; Cell Cycle - physiology; Cell Line; Cells; Cyclin B - genetics; Cyclin B - physiology; Cyclin B1; Deoxyribonucleic acid; DNA; Female; G2 Phase; Gene Expression Regulation; Genes, Reporter; Humans; Mice; Mitosis; Ovarian Neoplasms; Protein Kinases - metabolism; Recombinant Proteins - metabolism; Transfection; Tumor Cells, Cultured; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.5.2147

The p53 tumor suppressor controls multiple cell cycle checkpoints regulating 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°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 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 G 2 checkpoint has a role in preventing neoplastic transformation. cell cycle cdc2 mitosis cancer