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

Yunfei Huang, Daniel S. Higginson, Lynda Hester, Hee Park Myung, Solomon H. Snyder

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4194-4199
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number10
DOIs
StatePublished - Mar 6 2007

Keywords

  • Arginase
  • Deoxyhypusine synthase
  • Hypusine
  • Nerve growth factor
  • Spermidine

ASJC Scopus subject areas

  • General

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