Neuronal growth and survival mediated by eIF5A, a polyamine-modified translation initiation factor
Neuronal growth and survival mediated by eIF5A, a polyamine-modified translation initiation factor
复制标题
DOI：
10.1073/pnas.0611609104
复制
发表时间：
2007-03-06
影响因子：
11.1
通讯作者：
Snyder, Solomon H.
中科院分区：
文献类型：
--
作者：
Huang, Yunfei;Higginson, Daniel S.;Snyder, Solomon H.
真核翻译起始因子5A（eIF5A）是唯一已知的含有多胺衍生的氨基酸羟腐胺赖氨酸的蛋白质，调节蛋白质合成。我们发现，神经生长因子（NGF）的神经营养和神经保护作用是由hypusinated的eIF5A介导的，这可以解释已知的多胺在细胞生长和存活中的作用。PC12细胞的NGF处理刺激eIF5A形成。此外，通过脱氧羟腐胺赖氨酸合成酶的选择性抑制剂和通过RNA干扰的消耗来防止羟腐胺赖氨酸形成，阻断了NGF引起的PC12细胞的神经突生长和细胞存活的增强。在脑培养物中，羟腐胺赖氨酸形成的抑制也抑制神经元突起延伸。
Eukaryotic translation initiation factor 5A (elF5A) the only known protein containing the polyamine-derived amino acid hypusine, modulates protein synthesis. We show that neurotrophic and neuroprotective actions of nerve growth factor (NGF) are mediated by hypusinated elF5A, which can account for the known roles of polyamines in cell growth and survival. NGF treatment of PC12 cells stimulates elF5A formation. Moreover, prevention of hypusine formation by a selective inhibitor of deoxyhypusine synthase and by its depletion with RNA interference blocks the NGF-elicited augmentation of neurite outgrowth and cell survival of PC12 cells. In brain cultures, inhibition of hypusine formation also inhibits neuronal process extension.