A. Riccio et al., Mediation by a CREB family transcription factor of NGF-dependent survival of sympathetic neurons, SCIENCE, 286(5448), 1999, pp. 2358-2361
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.