Promiscuity Rules? The Dispensability of Cyclin E and Cdk2

The canonical view of the mammalian cell cycle arose from studies of cultured cells rather than mutant organisms. It depicts the many complexes of cyclin and Cdk (cyclin/Cdk) as fulfilling unique and essential steps that dictate the sequential order of cell cycle events. Recent analyses of knockout mice challenge this view. Cdk2 and cyclin E, long thought to be essential, are largely dispensable. Here, we discuss the phenotypes of these and other cyclin/Cdk mutants in genetically tractable metazoa (mouse, fly, and nematode) and explore possible reasons behind similarities and differences among experimental systems and cell types.