FOXO transcription factors directly activate bim gene expression and promote apoptosis in sympathetic neurons.
FOXO transcription factors directly activate bim gene expression and promote apoptosis in sympathetic neurons.
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FOXO转录因子直接激活BIM基因表达并促进交感神经元中的凋亡。
DOI：
10.1083/jcb.200303026
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发表时间：
2003-08-18
影响因子：
7.8
通讯作者：
Ham, Jonathan
中科院分区：
文献类型：
--
作者：
Gilley, Jonathan;Coffer, Paul J;Ham, Jonathan
发育中的交感神经元在缺乏NGF时通过凋亡而死亡。BIM是BCL-2家族中仅含BH 3的成员，在这些细胞中NGF撤除后诱导，并导致NGF撤除诱导的死亡。在这里，我们已经调查了参与的叉头盒，O类（FOXO）叉头转录因子的亚家族在调节BIM表达的神经生长因子。我们发现，FOXO转录因子的过度表达诱导BIM表达，促进交感神经元的死亡，在BIM依赖的方式。此外，我们发现，FKHRL 1（FOXO 3a）直接激活bim启动子通过两个保守的FOXO结合位点和这些网站的突变废除后，神经生长因子撤出bim启动子激活。最后，我们表明，FOXO活性有助于神经生长因子剥夺诱导的交感神经元死亡。
Developing sympathetic neurons die by apoptosis when deprived of NGF. BIM, a BH3-only member of the BCL-2 family, is induced after NGF withdrawal in these cells and contributes to NGF withdrawal–induced death. Here, we have investigated the involvement of the Forkhead box, class O (FOXO) subfamily of Forkhead transcription factors in the regulation of BIM expression by NGF. We find that overexpression of FOXO transcription factors induces BIM expression and promotes death of sympathetic neurons in a BIM-dependent manner. In addition, we find that FKHRL1 (FOXO3a) directly activates the bim promoter via two conserved FOXO binding sites and that mutation of these sites abolishes bim promoter activation after NGF withdrawal. Finally, we show that FOXO activity contributes to the NGF deprivation–induced death of sympathetic neurons.