Targeted disruption of p70s6kdefines its role in protein synthesis and rapamycin sensitivity

Publisher Website
Google Scholar
Abstract
Here, we disrupted the p70 S6 kinase (p70s6k) gene in murine embryonic stem cells to determine the role of this kinase in cell growth, protein synthesis, and rapamycin sensitivity. p70s6k−/− cells proliferated at a slower rate than parental cells, suggesting that p70s6k has a positive influence on cell proliferation but is not essential. In addition, rapamycin inhibited proliferation of p70s6k−/− cells, indicating that other events inhibited by the drug, independent of p70s6k, also are important for both cell proliferation and the action of rapamycin. In p70s6k−/− cells, which exhibited no ribosomal S6 phosphorylation, translation of mRNA encoding ribosomal proteins was not increased by serum nor specifically inhibited by rapamycin. In contrast, rapamycin inhibited phosphorylation of initiation factor 4E-binding protein 1 (4E-BP1), general mRNA translation, and overall protein synthesis in p70s6k−/− cells, indicating that these events proceed independently of p70s6k activity. This study localizes the function of p70s6k to ribosomal biogenesis by regulating ribosomal protein synthesis at the level of mRNA translation.