Although yeast need only one cdk to turn the cell cycle, the standard view was that mammals depend on at least five. Cdk2, Cdk3, Cdk4, and Cdk6 push the cell through interphase, whereas Cdk1 nudges it into mitosis. However, recent studies suggest otherwise. For example, lab mice are missing Cdk3 due to a mutation, and they show developmental—but not cell cycle—defects if they also lack any other pair of cdks.
To find out whether one cdk can suffice in mammals, the researchers analyzed mouse embryos that only manufactured Cdk1. The animals appeared to develop normally until they were about 13 days old, when their liver cells began dying en masse. The animals failed to produce enough hematopoetic cells, and the heart wall was weak. The mice died, but they managed to pull off about 20 million cell divisions, suggesting that Cdk1 alone can propel the cell cycle. In vitro studies confirmed the finding. Fibroblasts from the embryos proliferated in culture, albeit slowly.
Although Cdk1 can drive the cell cycle without the other cdks, the reverse is not true. Cdk1 is crucial for the earliest steps of development, as the researchers showed by crossing animals that had only one working copy of the Cdk1 gene. Homozygous embryos without Cdk1 did not survive past the morula stage.
“The classical model [of cdk action] can't be sustained,” says Barbacid. However, the results don't mean that the other cdks are dispensable, he notes. They are essential for division in specific cell types, such as hematopoetic cells and cardiac muscle. The researchers now want to cross cdk knockout mice with cancer-prone mice to determine which of the proteins are essential for tumor growth.