Translational Control of p27 Kip1 Accumulation During the Cell Cycle

• DOI: 10.1126/science.271.5257.1861
• Publication Date: 2006-10-27T18:30:41Z
• Authors: Ludger Hengst; Steven I. Reed
• Keywords: 0301 basic medicine; Tumor Suppressor Proteins; Cell Cycle; Molecular Sequence Data; G1 Phase; Cell Cycle Proteins; Cyclin-Dependent Kinases; Cell Line; S Phase; 03 medical and health sciences; Protein Biosynthesis; Tumor Cells, Cultured; Humans; Amino Acid Sequence; Lovastatin; RNA, Messenger; Enzyme Inhibitors; Microtubule-Associated Proteins; Cyclin-Dependent Kinase Inhibitor p27; Half-Life; HeLa Cells

Cell cycle phase transitions in eukaryotic cells are driven by regulation of the activity of protein kinases known as cyclin-dependent kinases (Cdks). A broad spectrum Cdk-inhibitory activity associated with a 28-kilodalton protein (p28 Ick1 ) was induced in cells treated with the drug lovastatin or upon density-mediated growth arrest and was periodic in the cell cycle, with peak activity in G 1 . The p28 Ick1 protein was shown to be identical to p27 Kip1 , and the periodic or induced inhibitory activity resulted from a periodic accumulation of the protein. Variations in the amount of p27 protein occurred, whereas the abundance 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, although in density-arrested fibroblasts and thymidine-arrested HeLa cells the half-life of the protein was also changed.