Apoptosis induced in mammalian cells by small peptides that functionally antagonize the Rb-regulated E2F transcription factor.
A variety of studies implicate the E2F transcription factor as a critical regulator of the mammalian cell cycle. The E2F pathway is aberrant in most, if not all, human tumor cells; therefore, therapeutic regimes that modulate E2F activity may provide an approach for reinstating growth control in situations where normal physiological control is lost. To elucidate the role of E2F in the cell cycle and assess its value as a therapeutic target, we have introduced peptides that functionally antagonize E2F DNA binding activity into mammalian cells. Introduction of these peptides into mammalian tumor cells caused the rapid onset of apoptosis, an outcome that correlates with the inactivation of physiological E2F.
Bandara
L R
LR
Prolifix Ltd, London, UK.
Girling
R
R
La Thangue
N B
NB
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D002352:Carrier Proteins; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D019281:Dimerization; D050684:E2F Transcription Factors; D006801:Humans; D008322:Mammals; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010455:Peptides / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D014176:Protein Biosynthesis / Q000187:drug effects / Q000235:genetics; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D010455:Peptides; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors