Abstract
Cyclin-dependent kinases (Cdks) control the major cell cycle transitions in eukaryotic cells. On the basis of a variety of experiments where cyclin function either is impaired or enhanced, D-type cyclins as well as cyclins E and A have been linked to G1 and G1/S phase roles in mammalian cells. We therefore sought to determine if agents that block the G1/S phase transition do so at the level of regulating the Cdk activities associated with these cyclins. A variety of conditions that lead to G1 arrest were found to correlate with accumulation of G1-specific Cdk inhibitors, including treatment of fibroblasts with ionizing radiation, treatment of epithelial cells with TGF-beta, treatment of HeLa cells with the drug lovastatin, and removal of essential growth factors from a variety of different cell types. Mechanistically, inhibition of Cdks was found to involve the stoichiometric binding of Cdk inhibitor proteins. p21Waf1/Cip1 was associated with DNA damage induced arrest while p27Kip1/p28Ick1 accumulated under a variety of antiproliferative conditions.
Original language | English (US) |
---|---|
Pages (from-to) | 69-73 |
Number of pages | 5 |
Journal | Journal of Cell Science |
Volume | 107 |
Issue number | SUPPL. 18 |
DOIs | |
State | Published - 1994 |
Externally published | Yes |
Keywords
- Cdk
- Cell cycle
- Cyclin
- G
ASJC Scopus subject areas
- Cell Biology