Huang Yunfei, Higginson Daniel S, Hester Lynda, Park Myung Hee, Snyder Solomon H
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4194-9. doi: 10.1073/pnas.0611609104. Epub 2007 Feb 28.
Eukaryotic translation initiation factor 5A (eIF5A), 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 eIF5A, which can account for the known roles of polyamines in cell growth and survival. NGF treatment of PC12 cells stimulates eIF5A 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.
真核生物翻译起始因子5A（eIF5A）是唯一已知的含有多胺衍生氨基酸hypusine的蛋白质，它可调节蛋白质合成。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 eIF5A介导的，这可以解释多胺在细胞生长和存活中的已知作用。用NGF处理PC12细胞可刺激eIF5A的形成。此外，脱氧hypusine合酶的选择性抑制剂以及通过RNA干扰使其耗竭来阻止hypusine的形成，会阻断NGF诱导的PC12细胞神经突生长增强和细胞存活。在脑培养物中，抑制hypusine的形成也会抑制神经元突起的延伸。
