Unmasking the S-phase-promoting potential of cyclin B1.
In higher eukaryotes, the S phase and M phase of the cell cycle are triggered by different cyclin-dependent kinases (CDKs). For example, in frog egg extracts, Cdk1-cyclin B catalyzes entry into mitosis but cannot trigger DNA replication. Two hypotheses can explain this observation: Either Cdk1-cyclin B fails to recognize the key substrates of its S-phase-promoting counterparts, or its activity is somehow regulated to prevent it from activating DNA synthesis. Here, we show that Cdk1-cyclin B1 has cryptic S-phase-promoting abilities that can be unmasked by relocating it from the cytoplasm to the nucleus and moderately stimulating its activity. Subcellular localization of vertebrate CDKs and the control of their activity are thus critical factors for determining their specificity.
Moore
Jonathan D
JD
Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Herts EN6 3LD, UK.
Kirk
Jane A
JA
Hunt
Tim
T
D021581:Active Transport, Cell Nucleus; D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000494:pharmacology; D002457:Cell Extracts; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism* / Q000494:pharmacology; D056744:Cyclin B1; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication; D004789:Enzyme Activation; D008938:Mitosis; D009685:Nuclear Envelope / Q000378:metabolism; D019913:Nuclear Localization Signals; D010063:Ovum; D011494:Protein Kinases / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D016196:S Phase; D014162:Transfection; D014981:Xenopus; D020687:cdc25 Phosphatases / Q000378:metabolism / Q000494:pharmacology
D018797:Cell Cycle Proteins; D002457:Cell Extracts; D002843:Chromatin; D019926:Cyclin B; D056744:Cyclin B1; D019913:Nuclear Localization Signals; D011993:Recombinant Fusion Proteins; D004247:DNA; D011494:Protein Kinases; C102333:histone H1 kinase; D016203:CDC2 Protein Kinase; D020687:cdc25 Phosphatases