Publication Date:
1999-12-22
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Riccio, A -- Ahn, S -- Davenport, C M -- Blendy, J A -- Ginty, D D -- NS34814-04/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1999 Dec 17;286(5448):2358-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205-2185, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10600750" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Apoptosis
;
Axons/drug effects/metabolism
;
Brain-Derived Neurotrophic Factor/pharmacology
;
Cell Nucleus/metabolism
;
Cell Survival
;
Cells, Cultured
;
Cyclic AMP Response Element-Binding Protein/antagonists & inhibitors/*metabolism
;
*Gene Expression Regulation
;
Genes, bcl-2
;
Genetic Vectors
;
Nerve Growth Factor/*pharmacology
;
Neurons/*cytology/drug effects/metabolism
;
PC12 Cells
;
Promoter Regions, Genetic
;
Proto-Oncogene Proteins c-bcl-2/genetics/metabolism
;
Rats
;
Recombinant Fusion Proteins/metabolism
;
Signal Transduction
;
Sympathetic Nervous System/*cytology/drug effects/metabolism
;
Transfection
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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