TRANSLATIONAL CONTROL OF P27(KIP1) ACCUMULATION DURING THE CELL-CYCLE

Cell cycle phase transitions in eukaryotic cells are driven by regulat ion of the activity of protein kinases known as cyclin-dependent kinas es (Cdks). A broad spectrum Cdk-inhibitory activity associated with a 28-kilodalton protein (p28(lck1)) was induced in cells treated with th e drug lovastatin or upon density-mediated growth arrest and was perio dic in the cell cycle, with peak activity in G(1). The p28(lck1) prote in was shown to be identical to p27(Kip1), and the periodic or induced inhibitory activity resulted from a periodic accumulation of the prot ein. Variations in the amount of p27 protein occurred, whereas the abu ndance of the p27 messenger RNA remained unchanged. In every instance investigated, the posttranscriptional alteration of p27 protein levels was achieved in part by a mechanism of translational control, althoug h in density-arrested fibroblasts and thymidine-arrested HeLa cells th e half-life of the protein was also changed.