Proceedings of the National Academy of Sciences · 1999 · 319 citations · 31 references
Life SciencesCancer BiologyOncologyApoptosisMolecular Cell BiologyMolecular OncologyApoptosis In CancerApoptosis RegulationApoptosis ResistanceApoptotic SignalingCyclin-dependent KinasesSynthetic LethalityAntineoplastic Drug TherapyCdk InhibitorsCyclin E FamilyCyclin-dependent Kinase ComplexesCyclin-dependent Kinase InhibitorsE2f Transcription ControlE2f Transcription Factor RegulationE2f Transcription Factors
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.
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Tat-mediated delivery of heterologous proteins into cells.
Stephen E. Fawell, J Seery, Yasmin Daikh et al. · Proceedings of the National Academy of Sciences · 1994 · 1.2K citations
Expression of transcription factor E2F1 induces quiescent cells to enter S phase
D. Gale Johnson, James K. Schwarz, W. Douglas Cress et al. · Nature · 1993 · 953 citations