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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We thank A. Kolodkin, R. Misra, F. Rupp, and members of the Ginty laboratory for helpful discussions and comments on this manuscript; A. Lanahan and P. Worley for advice with the reverse Northern experiment; B. Lonze for help with figures; A. Shaywitz and M. Greenberg for the CREB-VP16 constructs; M. Hardwick for discussions and Bcl-2 expression vectors; B. A. Tsui-Pierchala for advice with cytochrome c immunocytochemistry; and L. Boxer for Bcl-2–luciferase constructs. CREB mutant mice were provided by G. Schutz and the Deutsches Krebforschungzentrum. Supported by a Pew Scholars Award and NIH grant NS34814-04 (D.D.G.).

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Published In

Volume 286 | Issue 5448
17 December 1999

Submission history

Received: 4 June 1999
Accepted: 16 November 1999
Published in print: 17 December 1999


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Antonella Riccio
Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205–2185, USA.
Sohyun Ahn
Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205–2185, USA.
Christopher M. Davenport
Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205–2185, USA.
Julie A. Blendy
Department of Pharmacology, University of Pennsylvania Medical Center, Philadelphia, PA 19104–6084, USA.
David D. Ginty*
Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205–2185, USA.


To whom correspondence should be addressed. E-mail: [email protected]

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