Interleukin-2-mediated elimination of the p27Kip1 cyclin-dependent kinase inhibitor prevented by rapamycin.

Nature 1994 Dec;372(6506):570-3

Program in Cancer Biology, Stanford University Medical School, California 94305.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1038/372570a0DOI Listing
December 1994
1 Read

Publication Analysis

Top Keywords

cdk inhibitor
8
cyclin-dependent kinase
8
prevented rapamycin
8
cdk
5
mammals report
4
report il-2
4
yeast mammals
4
arrest yeast
4
cell-cycle arrest
4
il-2 allows
4
allows cdk
4
elimination cdk
4
causing elimination
4
activation causing
4
cdk activation
4
leading cell-cycle
4
signalling activates
4
complexes rapamycin
4
il-2 signalling
4
e/cdk2 complexes
4

References

(Supplied by CrossRef)

M Ohtsubo et al.
Science 1993

DE Quelle et al.
Genes Dev. 1993

EJ Firpo et al.
Molec. cell. Biol. 1994

FJ Dumont et al.
J. Immun. 1990

J Kunz et al.
Trends biol. Sci. 1994

EJ Brown et al.
Nature 1994

DM Sabatini et al.
Cell 1994

WG Morice et al.
J. biol. Chem. 1993

JW Harper et al.
Cell 1993

Y Xiong et al.
Nature 1993

Y Gu et al.
Nature 1993

Similar Publications