Complete inhibition of Cdk/cyclin by one molecule of p21Cip1

摘要: Cell-cycle phase transitions are controlled by cyclin-dependent kinases (Cdks). Key to the regulation of these kinase activities Cdk inhibitors, proteins that induced in response various antiproliferative signals but can also oscillate during cell-cycle progression, leading inactivation. A current dogma is complexes containing prototype inhibitor p21 transit between active and inactive states, associated with one molecule remain until they associate additional molecules. However, using a number different techniques including analytical ultracentrifugation purified p21/cyclin A/Cdk2 we demonstrate unambiguously single sufficient for inhibition p21-saturated contain only stably bound molecule. Even phosphorylated forms efficient inhibitors activities. Therefore level inactivation determined fraction complexed not stoichiometry or phosphorylation state inhibitor.