Abstract
Transforming growth factor β (TGF-β) is a potent inhibitor of epithelial cell growth. Cyclins E and A in association with Cdk2 have been shown to play a role in the G1-to-S phase transition in mammalian cells. We have studied the effects of TGF-β-mediated growth arrest on G1/S cyclins E and A. Inhibition of cyclin A-associated kinase by TGF-β is primarily due to a decrease in cyclin A mRNA and protein. By contrast, while TGF-β inhibits accumulation of cyclin E mRNA, the reduction in cyclin E protein is minimal. Instead, we find that the activation of cyclin E-associated kinase that normally accompanies the G1-to-S phase transition is inhibited. A novel inhibitor of cyclin-Cdk complexes was detected in TGF-β-treated cell lysates. Inhibition is mediated by a heat-stable protein that targets both Cdk2 and Cdc2 kinases. In G0-arrested cells, a similar inhibitor of Cdk2 kinase was detected. These data suggest the existence of an inhibitor of cyclin-dependent kinases induced under different conditions to mediate antiproliferative responses.
Original language | English (US) |
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Pages (from-to) | 3683-3694 |
Number of pages | 12 |
Journal | Molecular and cellular biology |
Volume | 14 |
Issue number | 6 |
DOIs | |
State | Published - Jun 1994 |
Externally published | Yes |
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology