Cell Cycle Control: A Complex Issue

Do p27Kip1 and p21Cip1 function as activators or inhibitors of D cyclin-cdk4 activity? Attempts to answer this question and thus to understand how cdk4—a key cell cycle regulator—becomes active have produced conflicting data. In this perspective, we summarize the results of studies addressing the effects of p27Kip1 and p21Cip1 on the assembly and activation of D cyclin-cdk4 complexes. Emphasis is placed on our experimental findings, which support a model of cell cycle control in which p27Kip1 and p21Cip1 stabilize D cyclin-cdk4 complexes but inhibit D cyclin-cdk4 activity.