COOPERATION BETWEEN THE CDK INHIBITORS P27(KIP1) AND P57(KIP2) IN THECONTROL OF TISSUE-GROWTH AND DEVELOPMENT

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 re gulated by cyclin-dependent kinases (Cdks). The main effecters that do wnregulate Cdk activity to activate Rb are not known in the lens or ot her tissues. In this study, using multiple mutant mice, we show that t he Cdk inhibitors p27(KIP1) and p57(KIP2) function redundantly to cont rol cell cycle exit and differentiation of lens fiber cells and placen tal trophoblasts. These studies demonstrate that p27(KIP1) and p57(KIP 2) are critical terminal effecters of signal transduction pathways tha t control cell differentiation.