Selective killing of transformed cells by cyclin/cyclin-dependent kinase 2 antagonists
YNP Chen, SK Sharma, TM Ramsey… - Proceedings of the …, 1999 - National Acad Sciences
Proceedings of the National Academy of Sciences, 1999•National Acad Sciences
Recent studies identified a short peptide motif that serves as a docking site for cyclin/cyclin-
dependent kinase (cdk) 2 complexes. Peptides containing this motif block the
phosphorylation of substrates by cyclin A/cdk2 or cyclin E/cdk2. Here we report that cell
membrane-permeable forms of such peptides preferentially induced transformed cells to
undergo apoptosis relative to nontransformed cells. Deregulation of E2F family transcription
factors is a common event during transformation and was sufficient to sensitize cells to the …
dependent kinase (cdk) 2 complexes. Peptides containing this motif block the
phosphorylation of substrates by cyclin A/cdk2 or cyclin E/cdk2. Here we report that cell
membrane-permeable forms of such peptides preferentially induced transformed cells to
undergo apoptosis relative to nontransformed cells. Deregulation of E2F family transcription
factors is a common event during transformation and was sufficient to sensitize cells to the …
Recent studies identified a short peptide motif that serves as a docking site for cyclin/cyclin-dependent kinase (cdk) 2 complexes. Peptides containing this motif block the phosphorylation of substrates by cyclin A/cdk2 or cyclin E/cdk2. Here we report that cell membrane-permeable forms of such peptides preferentially induced transformed cells to undergo apoptosis relative to nontransformed cells. Deregulation of E2F family transcription factors is a common event during transformation and was sufficient to sensitize cells to the cyclin/cdk2 inhibitory peptides. These results suggest that deregulation of E2F and inhibition of cdk2 are synthetically lethal and provide a rationale for the development of cdk2 antagonists as antineoplastic agents.
National Acad Sciences
