title: Sustained accumulation of the mitotic cyclins and tyrosine-phosphorylated p34cdc2 in human G1-S-arrested cancer cells but not untransformed cells.
abstract: Coupling mitosis to the completion of DNA replication in cycling embryonic extracts from Xenopus eggs appears to rely on blocking the activation of the tyrosine-phosphorylated p34cdc2/cyclin B, which continues to build up when S phase is inhibited by adding unreplicated DNA (Smythe, C., and Newport, J. W., Cell, 68: 787-797, 1992). We show here that a similar mechanism might be operative in human tumor-derived cells, which, during a thymidine-aphidicolin block, stop progressing through S phase and thereby fail to undergo mitosis. Under such conditions, indeed, cancer cells do continue to accumulate cyclin A, cyclin B1, and tyrosine-phosphorylated p34cdc2 to supranormal levels, a phenomenon that does not occur in untransformed, nonimmortalized human fibroblasts. Thus, in human cancer cells, the onset of active accumulation of cyclin A and cyclin B1 can be uncoupled from transit through the G1-S and S-G2 borders, respectively, and, as in simple embryonic cell cycles, the coupling of mitosis to the completion of S phase presumably relies, at least in part, on the prevention of premature activation of the tyrosine-phosphorylated p34cdc2/cyclin B1 complex.
authors.affiliation: Unité Mixte de Recherche 146 du Centre National de la Recherche Scientifique, Institut Curie-Recherche, Centre Universitaire, Orsay, France.
authors.forename: T
authors.initials: T
authors.lastname: David-Pfeuty
authors.forename: Y
authors.initials: Y
authors.lastname: Nouvian-Dooghe
mesh_terms: D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002453:Cell Cycle; D002461:Cell Line, Transformed; D019925:Cyclin A / Q000378:metabolism*; D019926:Cyclin B / Q000378:metabolism*; D056744:Cyclin B1; D005347:Fibroblasts / Q000166:cytology; D016193:G1 Phase; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D010766:Phosphorylation; D016196:S Phase; D014407:Tumor Cells, Cultured
chemical_list: C534699:CCNB1 protein, human; D019925:Cyclin A; D019926:Cyclin B; D056744:Cyclin B1; D016203:CDC2 Protein Kinase