Mediation by a CREB family transcription factor of NGF-dependent survival of sympathetic neurons
Mediation by a CREB family transcription factor of NGF-dependent survival of sympathetic neurons
复制标题
DOI：
10.1126/science.286.5448.2358
复制
发表时间：
1999-12-17
期刊：
影响因子：
56.9
通讯作者：
Ginty, DD
中科院分区：
文献类型：
--
作者：
Riccio, A;Ahn, S;Ginty, DD
神经生长因子（NGF）和其他神经营养因子通过不完全理解的过程支持神经元的存活。转录因子CREB是神经生长因子依赖性基因表达的关键介质，但CREB家族转录因子是否调节有助于交感神经元神经生长因子依赖性存活的基因的表达尚不清楚。CREB介导的基因表达对神经生长因子依赖的交感神经元的存活是必需的，并且其本身足以促进交感神经元的存活。此外，Bcl-2的表达通过CREB依赖的转录机制被神经生长因子和其他神经营养因子激活。Bcl-2的过表达降低了CREB抑制的促死作用。总之，这些数据支持一种模型，其中神经营养因子促进神经元的存活，部分通过涉及CREB家族转录因子依赖性表达的基因编码促生存因子的机制。
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.