Interleukin-2-mediated elimination of the p27Kip1 cyclin-dependent kinase inhibitor prevented by rapamycin
| Autor: | J, Nourse, E, Firpo, W M, Flanagan, S, Coats, K, Polyak, M H, Lee, J, Massague, G R, Crabtree, J M, Roberts |
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| Rok vydání: | 1994 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Sirolimus T-Lymphocytes Tumor Suppressor Proteins Cell Cycle Cyclin-Dependent Kinase 2 Cell Cycle Proteins Polyenes Protein Serine-Threonine Kinases Cyclin-Dependent Kinases Cell Line Enzyme Activation Fungal Proteins Mice Cyclins CDC2-CDC28 Kinases Animals Interleukin-2 Microtubule-Associated Proteins Cyclin-Dependent Kinase Inhibitor p27 Immunosuppressive Agents |
| Zdroj: | Nature. 372(6506) |
| ISSN: | 0028-0836 |
| Popis: | 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 cycle. 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 complexes. Rapamycin is a potent immunosuppressant which specifically inhibits G1-to-S-phase progression, leading to cell-cycle arrest in yeast and mammals. 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 p27Kip1 governs Cdk activity during the transition from quiescence to S phase in T lymphocytes and that p21 function may be restricted to cycling cells. |
| Databáze: | OpenAIRE |
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