Cooperation between the Cdk inhibitors p27KIP1 and p57KIP2 in the control of tissue growth and development

Abstract

Cell cycle exit is required for terminal differentiation of many cell types. The retinoblastoma protein Rb has been implicated both in cell cycle exit and differentiation in several tissues.Rb is negatively regulated by cyclin-dependent kinases (Cdks). The main effectors that down-regulate Cdkactivity to activate Rb are not known in the lens or other tissues. In this study, using multiple mutant mice, we show that theCdk inhibitors p27KIP1 andp57KIP2 function redundantly to control cell cycle exit and differentiation of lens fiber cells and placental trophoblasts. These studies demonstrate that p27KIP1and p57KIP2 are critical terminal effectors of signal transduction pathways that control cell differentiation.