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Science. 1993 Apr 23;260(5107):536-9.

Negative regulation of G1 in mammalian cells: inhibition of cyclin E-dependent kinase by TGF-beta.

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  • 1Department of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.

Abstract

Transforming growth factor-beta (TGF-beta) is a naturally occurring growth inhibitory polypeptide that arrests the cell cycle in middle to late G1 phase. Cells treated with TGF-beta contained normal amounts of cyclin E and cyclin-dependent protein kinase 2 (Cdk2) but failed to stably assemble cyclin E-Cdk2 complexes or accumulate cyclin E-associated kinase activity. Moreover, G1 phase extracts from TGF-beta-treated cells did not support activation of endogenous cyclin-dependent protein kinases by exogenous cyclins. These effects of TGF-beta, which correlated with the inhibition of retinoblastoma protein phosphorylation, suggest that mammalian G1 cyclin-dependent kinases, like their counterparts in yeast, are targets for negative regulators of the cell cycle.

PMID:
8475385
[PubMed - indexed for MEDLINE]
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