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.
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