Nature Biotechnology
15, 896 - 901 (1997)
doi:10.1038/nbt0997-896
Apoptosis induced in mammalian cells by small peptides that functionally antagonize the Rb-regulated E2F transcription factorLasantha R. Bandara1, Rowena Girling2
& Nicholas B. La Thangue1, 3, *
1Prolifix Ltd 1−3 Burtonhole Lane, Mill Hill, London NW71AD, UK
2Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Davidson Building, Glasgow G12 8QQ, UK.
3Laboratory of Eukaryotic Molecular Genetics, MRC National Institute for Medical Research, TheRidgeway, Mill Hill, London NW71AA, UK.
*Corresponding author (e-mail: n.lathangue@bio.gla.ac.uk). 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.
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