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Science 17 December 1999:
Vol. 286. no. 5448, pp. 2358 - 2361
DOI: 10.1126/science.286.5448.2358
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Reports

Mediation by a CREB Family Transcription Factor of NGF-Dependent Survival of Sympathetic Neurons

Antonella Riccio, 1 Sohyun Ahn, 1 Christopher M. Davenport, 1 Julie A. Blendy, 2 David D. Ginty 1*

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.

1 Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205-2185, USA.
2 Department of Pharmacology, University of Pennsylvania Medical Center, Philadelphia, PA 19104-6084, USA.
*   To whom correspondence should be addressed. E-mail: dginty{at}jhmi.edu

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The Herpes Simplex Virus Type 2 R1 Protein Kinase (ICP10 PK) Functions as a Dominant Regulator of Apoptosis in Hippocampal Neurons Involving Activation of the ERK Survival Pathway and Upregulation of the Antiapoptotic Protein Bag-1.
D. Perkins, E. F. R. Pereira, and L. Aurelian (2002)
J. Virol. 77, 1292-1305
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ERK1/2 Antagonizes Glycogen Synthase Kinase-3beta -induced Apoptosis in Cortical Neurons.
M. Hetman, S.-L. Hsuan, A. Habas, M. J. Higgins, and Z. Xia (2002)
J. Biol. Chem. 277, 49577-49584
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Nitric Oxide Protects Neuroblastoma Cells from Apoptosis Induced by Serum Deprivation through cAMP-response Element-binding Protein (CREB) Activation.
E. Ciani, S. Guidi, G. Della Valle, G. Perini, R. Bartesaghi, and A. Contestabile (2002)
J. Biol. Chem. 277, 49896-49902
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Localization of Phosphorylated cAMP Response Element-Binding Protein in Immature Neurons of Adult Hippocampus.
S. Nakagawa, J.-E. Kim, R. Lee, J. Chen, T. Fujioka, J. Malberg, S. Tsuji, and R. S. Duman (2002)
J. Neurosci. 22, 9868-9876
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Dopamine Induces a PI3-Kinase-Independent Activation of Akt in Striatal Neurons: A New Route to cAMP Response Element-Binding Protein Phosphorylation.
K. Brami-Cherrier, E. Valjent, M. Garcia, C. Pages, R. A. Hipskind, and J. Caboche (2002)
J. Neurosci. 22, 8911-8921
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Age-Dependent Resistance to Lethal Alphavirus Encephalitis in Mice: Analysis of Gene Expression in the Central Nervous System and Identification of a Novel Interferon-Inducible Protective Gene, Mouse ISG12.
L. Labrada, X. H. Liang, W. Zheng, C. Johnston, and B. Levine (2002)
J. Virol. 76, 11688-11703
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Receptor for Advanced Glycation End Products (RAGE) Signaling Induces CREB-dependent Chromogranin Expression during Neuronal Differentiation.
H. J. Huttunen, J. Kuja-Panula, and H. Rauvala (2002)
J. Biol. Chem. 277, 38635-38646
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Essential Role of cAMP-response Element-binding Protein Activation by A2A Adenosine Receptors in Rescuing the Nerve Growth Factor-induced Neurite Outgrowth Impaired by Blockage of the MAPK Cascade.
H.-C. Cheng, H.-M. Shih, and Y. Chern (2002)
J. Biol. Chem. 277, 33930-33942
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TrkA as a Life and Death Receptor: Receptor Dose as a Mediator of Function.
C. Yan, Y. Liang, K. D. Nylander, and N. F. Schor (2002)
Cancer Res. 62, 4867-4875
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Amyloid Precursor Protein Family-induced Neuronal Death Is Mediated by Impairment of the Neuroprotective Calcium/Calmodulin Protein Kinase IV-dependent Signaling Pathway.
C. Mbebi, V. See, L. Mercken, L. Pradier, U. Muller, and J.-P. Loeffler (2002)
J. Biol. Chem. 277, 20979-20990
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Bimodal regulation of mPeriod promoters by CREB-dependent signaling and CLOCK/BMAL1 activity.
Z. Travnickova-Bendova, N. Cermakian, S. M. Reppert, and P. Sassone-Corsi (2002)
PNAS 99, 7728-7733
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Parathyroid Hormone and Parathyroid Hormone-related Protein Exert Both Pro- and Anti-apoptotic Effects in Mesenchymal Cells.
H.-L. Chen, B. Demiralp, A. Schneider, A. J. Koh, C. Silve, C.-Y. Wang, and L. K. McCauley (2002)
J. Biol. Chem. 277, 19374-19381
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Brain-Derived Neurotrophic Factor Is Essential for Opiate-Induced Plasticity of Noradrenergic Neurons.
S. Akbarian, M. Rios, R.-J. Liu, S. J. Gold, H.-F. Fong, S. Zeiler, V. Coppola, L. Tessarollo, K. R. Jones, E. J. Nestler, et al. (2002)
J. Neurosci. 22, 4153-4162
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Pincher, a pinocytic chaperone for nerve growth factor/TrkA signaling endosomes.
Y. Shao, W. Akmentin, J. J. Toledo-Aral, J. Rosenbaum, G. Valdez, J. B. Cabot, B. S. Hilbush, and S. Halegoua (2002)
J. Cell Biol. 157, 679-691
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Expression of cyclic adenosine monophosphate response-element binding protein in acute leukemia.
H. N. Crans-Vargas, E. M. Landaw, S. Bhatia, G. Sandusky, T. B. Moore, and K. M. Sakamoto (2002)
Blood 99, 2617-2619
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Activating Transcription Factor 1 and CREB Are Important for Cell Survival during Early Mouse Development.
S. C. Bleckmann, J. A. Blendy, D. Rudolph, A. P. Monaghan, W. Schmid, and G. Schutz (2002)
Mol. Cell. Biol. 22, 1919-1925
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The Mitochondrial Toxin 3-Nitropropionic Acid Induces Striatal Neurodegeneration via a c-Jun N-Terminal Kinase/c-Jun Module.
M. Garcia, P. Vanhoutte, C. Pages, M.-J. Besson, E. Brouillet, and J. Caboche (2002)
J. Neurosci. 22, 2174-2184
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Dominant-negative Suppression of HNF-1alpha Results in Mitochondrial Dysfunction, INS-1 Cell Apoptosis, and Increased Sensitivity to Ceramide-, but Not to High Glucose-induced Cell Death.
H. Wobser, H. Du{beta}mann, D. Kogel, H. Wang, C. Reimertz, C. B. Wollheim, M. M. Byrne, and J. H. M. Prehn (2002)
J. Biol. Chem. 277, 6413-6421
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Phosphorylation of cAMP Response Element-Binding Protein in Hippocampal Neurons as a Protective Response after Exposure to Glutamate In Vitro and Ischemia In Vivo.
T. Mabuchi, K. Kitagawa, K. Kuwabara, K. Takasawa, T. Ohtsuki, Z. Xia, D. Storm, T. Yanagihara, M. Hori, and M. Matsumoto (2001)
J. Neurosci. 21, 9204-9213
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