Cyclin D2-CDK4/6 complex drives efficient hyperproliferation in Apc deficient cells. (A) In the normal intestinal epithelium Wnt activity and hence c-Myc levels are restricted. This prevents accumulation of the cyclin D2-CDK4/6 complex and suppresses proliferation. (B) In Apc deficient cells Wnt activity and c-Myc levels are high. The high levels of c-Myc lead to accumulation of cyclin D2 and CDK4/6, possibly via their direct transcriptional activation. The complex of cyclin D2 and CDK4/6 phosphorylates Rb and permits E2F to drive cell cycle entry and subsequent hyperproliferation.