Neuronal growth and survival mediated by eIF5A, a polyamine-modified translation initiation factor

被引：46
作者：
Huang, Yunfei
Higginson, Daniel S.
Hester, Lynda
Park, Myung Hee
Snyder, Solomon H.
机构：
[1] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA
[4] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2007年 / 104卷 / 10期
关键词：
hypusine; spermidine; nerve growth factor; arginase; deoxyhypusine synthase;
D O I：
10.1073/pnas.0611609104
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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.
引用
收藏
页码：4194 / 4199
页数：6
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