Sustained accumulation of the mitotic cyclins and tyrosine-phosphorylated p34cdc2 in human G1-S-arrested cancer cells but not untransformed cells.
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.
David-Pfeuty
T
T
Unité Mixte de Recherche 146 du Centre National de la Recherche Scientifique, Institut Curie-Recherche, Centre Universitaire, Orsay, France.
Nouvian-Dooghe
Y
Y
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
C534699:CCNB1 protein, human; D019925:Cyclin A; D019926:Cyclin B; D056744:Cyclin B1; D016203:CDC2 Protein Kinase