Interleukin-2-mediated elimination of the p27(Kip1) cyclin-dependent kinase inhibitor prevented by rapamycin Journal Article

  

Authors:	Nourse, J.; Firpo, E.; Flanagan, W. M.; Coats, S.; Polyak, K.; Lee, M. H.; Massague, J.; Crabtree, G. R.; Roberts, J. M.
Article Title:	Interleukin-2-mediated elimination of the p27(Kip1) cyclin-dependent kinase inhibitor prevented by rapamycin
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 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.
Keywords:	controlled study; nonhuman; t lymphocyte; t-lymphocytes; animal cell; animal; mammalia; mice; cell cycle; cell cycle s phase; interleukin 2; cell line; mitogenesis; enzyme activation; animalia; protein-serine-threonine kinases; cyclin-dependent kinases; cyclins; cyclin dependent kinase; protein p21; protein kinase; rapamycin; sirolimus; immunosuppressive agents; cell cycle g1 phase; immunosuppressive agent; interleukin-2; fungal proteins; microtubule-associated proteins; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; cell cycle parameters; polyenes; transferase inhibitor
Journal Title:	Nature
Volume:	372
Issue:	6506
ISSN:	0028-0836
Publisher:	Nature Publishing Group
Date Published:	1994-12-08
Start Page:	570
End Page:	573
Language:	English
DOI:	10.1038/372570a0
PROVIDER:	scopus
PUBMED:	7990932
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0028172867&doi=10.1038%2f372570a0&partnerID=40&md5=c865426f1ec98d907d9c467b2fcf3991
Notes:	Export Date: 14 January 2019 -- Article -- Source: Scopus

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