INTERLEUKIN-2-MEDIATED ELIMINATION OF THE P27(KIP1) CYCLIN-DEPENDENT KINASE INHIBITOR PREVENTED BY RAPAMYCIN

THE cyclin-dependent kinase (Cdk) enzymes, when associated with the G1 cycIins D and E, are rate-limiting for entry into the S phase of the cell cycle(1,2). During T-cell mitogenesis, antigen-receptor signallin g promotes synthesis of cyclin E and its catalytic partner, Cdk2, and interleukin-2 (IL-2) signalling activates cyclin E/Cdk2 complexes(3). Rapamycin is a potent immunosuppressant which specifically inhibits G1 -to-S-phase progression, leading to cell-cycle arrest in yeast and mam mals(4-7) Here we report that IL-2 allows Cdk activation by causing th e elimination of the Cdk inhibitor protein p27(Kip1), 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 p27(Kip1) governs Cdk activity during the transition from quiesce nce to S phase in T lymphocytes and that p21 function may be restricte d to cycling cells.