CELL CYCLE:Order from Destruction

Cyclin E and its kinase partner CDK2 are essential for initiating duplication of the genome during S phase of the cell cycle. But how is cyclin E itself regulated? In a comprehensive Perspective, Bartek and Lukas describe new findings in this issue and elsewhere that identify an F-box protein called Fbw7/hCdc4/Ago as the controller of cyclin E degradation. Intriguingly, mutations in this F-box protein are associated with some forms of breast and ovarian cancer.