Abstract
Apoptosis of human endothelial cells after growth factor deprivation is associated with rapid and dramatic up-regulation of cyclin A-associated cyclin-dependent kinase 2 (cdk2) activity. In apoptotic cells, the C termini of the cdk inhibitors P21Clp1/Waf1 and p27Klp1 are truncated by specific cleavage. The enzyme involved in this cleavage is CPP32 and/or a CPP32-like caspase. After cleavage, p21Clp1/Waf1 loses its nuclear localization sequence and exits the nucleus. Cleavage of p21Clp1/Waf1 and p27Klp1 results in a substantial reduction in their association with nuclear cyclin-cdk2 complexes, leading to a dramatic induction of cdk2 activity. Dominant-negative cdk2, as well as a mutant of P2Clp1/Waf1 resistant to caspase cleavage, partially suppress apoptosis. These data suggest that cdk2 activation, through caspase-mediated cleavage of cdk inhibitors, may be instrumental in the execution of apoptosis following caspase activation.
Original language | English (US) |
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Pages (from-to) | 553-563 |
Number of pages | 11 |
Journal | Molecular cell |
Volume | 1 |
Issue number | 4 |
DOIs | |
State | Published - Mar 1998 |
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology