Selective killing of transformed cells by cyclin/cyclin-dependent kinase 2 antagonists
AUTOR(ES)
Chen, Ying-Nan P.
FONTE
The National Academy of Sciences
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=16331Documentos Relacionados
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