Clinical CDK4/6 inhibitors induce selective and immediate dissociation of p21 from cyclin D-CDK4 to inhibit CDK2

Abstract

Clinical CDK4/6 inhibitors are used and tested to treat a variety of cancer types. Here, the authors identify that these drugs work in two ways, a known catalytic role to inhibit kinase activity and a newly discovered noncatalytic role to displace CDK inhibitor p21 from CDK4 but not CDK6 complexes.