title: p53-independent induction of apoptosis by cyclin-dependent kinase inhibition.
abstract: 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.
authors.affiliation: Department of Radiology, Nagasaki University, School of Dentistry, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Shibata
authors.forename: S
authors.initials: S
authors.lastname: Nishimura
authors.forename: A
authors.initials: A
authors.lastname: Okuyama
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
mesh_terms: 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*
chemical_list: D004791:Enzyme Inhibitors; D016159:Tumor Suppressor Protein p53; C082868:butyrolactone I; D018844:Cyclin-Dependent Kinases; D015107:4-Butyrolactone