The transcription factor E2F1 modulates apoptosis of neurons

The transcription factor E2F1 is known to mediate apoptosis in isolated qui escent and postmitotic cardiac myocytes, and its absence decreases the size of brain infarction following cerebral ischemia. To demonstrate directly t hat E2F1 modulates neuronal apoptosis, we used cultured cortical neurons to show a temporal association of the transcription and expression of E2F1 in neurons with increased neuronal apoptosis. Cortical neurons lacking E2F1 e xpression (derived from E2F1 -/- mice) were resistant to staurosporine-indu ced apoptosis as evidenced by the significantly lower caspase 3-like activi ty and a lesser number of cells with apoptotic morphology in comparison wit h cortical cultures derived from wild-type mice. Furthermore, overexpressin g E2F1 alone using replication-deficient recombinant adenovirus was suffici ent to cause neuronal cell death by apoptosis, as evidenced by the appearan ce of hallmarks of apoptosis, such as the threefold increase in caspase 9-l ike activity and increased laddered DNA fragmentation, in situ end-labeled DNA fragmentation, and numbers of neuronal cells with punctate nuclei. Take n together, we conclude that E2F1 plays a key role in modulating neuronal a poptosis.