Abstract
THE cyclin-dependent kinase (Cdk) enzymes, when associated with the G1 cyclins D and E, are rate-limiting for entry into the S phase of the cell cycle1,2. During T-cell mitogenesis, antigen–receptor signalling promotes synthesis of cyclin E and its catalytic partner, Cdk2, and interleukin-2 (IL-2) signalling activates cyclin E/Cdk2 complexes3. Rapamycin is a potent immunosuppressant which specifically inhibits Gl-to-S-phase progression, leading to cell-cycle arrest in yeast and mammals4–7. Here we report that IL-2 allows Cdk activation by causing the elimination of the Cdk inhibitor protein p27Kip1, and that this is prevented by rapamycin. By contrast, the Cdk inhibitor p21 is induced by IL-2 and this induction is blocked by rapamycin. Our results show that p27Kiplgoverns Cdk activity during the transition from quiescence to S phase in T lymphocytes and that p21 function may be restricted to cycling cells.
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Nourse, J., Firpo, E., Flanagan, W. et al. lnterleukin-2-mediated elimination of the p27Kipl cyclin-dependent kinase inhibitor prevented by rapamycin. Nature 372, 570–573 (1994). https://doi.org/10.1038/372570a0
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DOI: https://doi.org/10.1038/372570a0
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