p53-independent induction of apoptosis by cyclin-dependent kinase inhibition.
The G1 checkpoint and terminal differentiation may be associated with apoptosis, the induction of which is in large part dependent on the presence of active p53. However, cells lacking wild-type p53 can undergo apoptotic cell death during normal development and during terminal differentiation of malignant cells. Using the specific inhibitor for cyclin-dependent kinases (cdks), we show here that an inhibition of cdk activity per se can induce apoptotic cell death during G1-S transition of the cell cycle in a p53-independent manner. The apoptotic process triggered by cdk inhibition was associated with an overriding of the G1-S boundary and was inhibited by arresting the cells in G1. These results raise the possibility that aberrant cell cycle machinery may result in self-elimination, even in the absence of p53, and further indicate that cdk activity is not necessarily required during this process.
Shibata
Y
Y
Department of Radiology, Nagasaki University, School of Dentistry, Japan.
Nishimura
S
S
Okuyama
A
A
Nakamura
T
T
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D004791:Enzyme Inhibitors; D016159:Tumor Suppressor Protein p53; C082868:butyrolactone I; D018844:Cyclin-Dependent Kinases; D015107:4-Butyrolactone