Cell cycle progression without cyclin E/CDK2: breaking down the walls of dogma.

G1 is the phase of the cell cycle wherein the cell is responsive to growth factor-dependent signals. As such, G1 regulation is frequently disrupted in cancer through deregulation of cyclin/CDK activity; deregulation of G1 phase provides tumorigenic cells with a growth advantage. Cyclin E, the regulatory cyclin for CDK2, is considered a requisite regulator of G1 progression. Cyclin E is overexpressed in cancer, suggesting that cyclin E/CDK2 deregulation contributes to tumorigenesis. Two papers now challenge both the concept that cyclin E/CDK2 is a requisite component of the cell cycle machine and efforts to develop cyclin E/CDK2 inhibitors as antiproliferative therapeutics.