Life and death decisions by E2F-1

Deregulation of the transcription factor E2F-1 is a common event in most human cancers. Paradoxically, E2F-1 has been shown to have the ability to induce both cell cycle progression and programmed cell death, leading potentially to both tumour-promoting as well as tumour-suppressive effects. Although the pathway to cell cycle progression seems straightforward with a number of growth-promoting E2F target genes having been described, the pathways to apoptosis are less well defined and more complex. The discovery that E2F-1 ‘knockout’ mice are highly tumour prone has caused a recent surge in the number of reports relating to programmed cell death. This review focuses on these recent findings, highlighting the way in which they have increased our understanding of E2F-1-induced cell death, as well as indicating the questions that remain. Insight gained as to the role of this intriguing molecule in cancer and its potential for targeted therapy will also be discussed.