Inhibitors of mammalian G1 cyclin-dependent kinases.

Biologic machines need brakes, and the nature and fidelity of their operation cannot be unraveled without some prior understanding of how accelerators work. The discoveD] of mammalian G1 cyclins just 4 years ago and the identification of their associated cyclin-dependent kinases (cdks) provided key insights soon thereafter as to how progression through the first gap phase (G~) of the mammalian cell cycle might be regulated positively. Within the past 18 months, we have begun to learn something about the negative regulators--cdk inhibitors--that constrain their action.

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