Translational control of p27Kip1 accumulation during the cell cycle.
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 of Cdk-inhibitory activity associated with a 28-kilodalton protein (p28lck1) 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 G1. The p28lck1 protein was shown to be identical to p27Kip1, 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.
Hengst
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Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
Reed
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SI
D000595:Amino Acid Sequence; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002460:Cell Line; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000378:metabolism; D016193:G1 Phase; D006207:Half-Life; D006367:HeLa Cells; D006801:Humans; D008148:Lovastatin / Q000494:pharmacology; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016196:S Phase; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D008148:Lovastatin; D018844:Cyclin-Dependent Kinases