A C-JUN DOMINANT-NEGATIVE MUTANT PROTECTS SYMPATHETIC NEURONS AGAINST PROGRAMMED CELL-DEATH
A C-JUN DOMINANT-NEGATIVE MUTANT PROTECTS SYMPATHETIC NEURONS AGAINST PROGRAMMED CELL-DEATH
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DOI：
10.1016/0896-6273(95)90331-3
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发表时间：
1995-05-01
期刊：
影响因子：
16.2
通讯作者：
RUBIN, LL
中科院分区：
文献类型：
--
作者：
HAM, J;BABIJ, C;RUBIN, LL
交感神经元的生存依赖于神经生长因子（NGF），如果没有神经生长因子，交感神经元就会因细胞凋亡而死亡。我们使用每个家族成员特异的抗体研究了 Jun 和 Fos 转录因子家族在垂死交感神经元中的表达模式。当交感神经元缺乏 NGF 时，c-Jun 蛋白的水平显着增加，而 Jun 和 Fos 家族其他成员的水平保持相对恒定。 c-Jun 也变得更加磷酸化，可能是在其氨基末端反式激活结构域上。当显微注射到交感神经元时，c-Jun 显性失活突变体的表达载体可以保护它们免受 NGF 撤退诱导的死亡，表明 AP-1 活性对于神经元细胞死亡至关重要。此外，全长c-Jun蛋白的过度表达本身足以诱导交感神经元凋亡。
Sympathetic neurons depend on nerve growth factor (NGF) for survival and die by apoptosis in its absence. We have investigated the pattern of expression of the Jun and Fos family of transcription factors in dying sympathetic neurons using antibodies specific for each family member. When sympathetic neurons are deprived of NGF, the level of c-Jun protein significantly increases, whereas the levels of the other members of the Jun and Fos family remain relatively constant. c-Jun also becomes more phosphorylated, probably on its amino terminal transactivation domain. When microinjected into sympathetiic neurons, an expression vector for a c-Jun dominant negative mutant protects them against NGF withdrawal-induced death, indicating that AP-1 activity is essential for neuronal cell death. Furthermore, overexpression of the full-length c-Jun protein is, in itself, sufficient to induce apoptosis in sympathetic neurons.