After several groups reported discovering cyclin E and cyclin-dependent kinase 2 (CDK2) in 1991, a consensus emerged. It held that these protein partners are crucial in promoting the cell cycle's G1- to S-phase transition and driving cancer-cell proliferation. Therapeutically minded investigators accordingly began to seek inhibitors that would target CDK2's ATP-binding pocket and catalytic site.
But five recently published papers demolish this consensus view. Two researchers knocked down CDK2 protein expression in cancer cell lines, and the cells continued to divide.1 Four teams of scientists knocked out the CDK2 or cyclin E genes (CCNE1 and CCNE2), and the mice were viable, or their cells proliferated in culture.2-5 Many of the rodents, however, were sterile.
When Mariano Barbacid, director of the Spanish National Cancer Center in Madrid, heard that his newly generated CDK2-null mice were running around in the animal facility, "My first thought was, we've done something wrong," he says. ...
