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

Authors:
Riccio A, Ahn S, Davenport CM, Blendy JA, Ginty DD
Associated Labs:
Ginty Lab (Johns Hopkins University and School of Medicine)
Science. 1999 Dec 17. 286(5448):2358-61.
PMID: 10600750
Nerve growth factor (NGF) and other neurotrophins support survival of neurons through processes that are incompletely understood. The transcription factor CREB is a critical mediator of NGF-dependent gene expression, but whether CREB family transcription factors regulate expression of genes that contribute to NGF-dependent survival of sympathetic neurons is unknown. CREB-mediated gene expression was both necessary for NGF-dependent survival and sufficient 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 death-promoting effects of CREB inhibition. Together, these data support a model in which neurotrophins promote survival of neurons, in part through a mechanism involving CREB family transcription factor-dependent expression of genes encoding prosurvival factors.

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