Cdk2 is dispensable for cell cycle inhibition and tumor suppression mediated by p27Kip1 and p21Cip1

Summaryp27Kip1 and p21Cip1 are thought to suppress tumor growth and prevent cell cycle progression by inhibiting Cdk2-cyclin E/A kinases. Since Cdk2 is dispensable for mitotic cell division, we analyzed the activity of these inhibitors in Cdk2-deficient cells. Ectopic expression of p27Kip1 or p21Cip1 efficiently inhibits cell cycle progression of Cdk2−/− fibroblasts. Loss of p27Kip1 or p21Cip1 confers similar proliferative advantages to Cdk2+/+ and Cdk2−/− cells. Moreover, Cdk2 is dispensable for p21Cip1-induced cell cycle arrest after DNA damage. Finally, ablation of Cdk2 in p27Kip1 null mice does not suppress their phenotypic defects, including development of pituitary tumors. These results indicate that Cdk2 is not an essential target for p27Kip1 and p21Cip1 in cell cycle inhibition and tumor suppression