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

Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4194-9. doi: 10.1073/pnas.0611609104.

Yunfei Huang ¹, Daniel S Higginson, Lynda Hester, Myung Hee Park, Solomon H Snyder

Affiliations

Affiliation

1 Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.

PMID: 17360499 DOI: 10.1073/pnas.0611609104

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.

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