Mediation by a CREB family transcription factor of NGF-dependent survival of sympathetic neurons

Nerve growth factor (NGF) and other neurotrophins support survival of neuro ns through processes that are incompletely understood. The transcription fa ctor CREB is a critical mediator of NGF-dependent gene expression, but whet her CREB family transcription factors regulate expression of genes that con tribute to NGF-dependent survival of sympathetic neurons is unknown. CREB-m ediated gene expression was both necessary for NGF-dependent survival and s ufficient on its own to promote survival of sympathetic neurons, Moreover, expression of Bcl-2 was activated by NGF and other neurotrophins by a CREB- dependent transcriptional mechanism. Overexpression of Bcl-2 reduced the de ath-promoting effects of CREB inhibition. Together, these data support a mo del in which neurotrophins promote survival of neurons, in part through a m echanism involving CREB family transcription factor-dependent expression of genes encoding prosurvival factors.