Neuronal growth and survival mediated by eIF5A, a polyamine-modified translation initiation factor.
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.
Huang
Yunfei
Y
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Higginson
Daniel S
DS
Hester
Lynda
L
Park
Myung Hee
MH
Snyder
Solomon H
SH
D000818:Animals; D001119:Arginase / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D002852:Chromatography, Ion Exchange; D006624:Hippocampus / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D020932:Nerve Growth Factor / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D016716:PC12 Cells; D010448:Peptide Initiation Factors / Q000737:chemistry / Q000378:metabolism*; D011073:Polyamines / Q000737:chemistry* / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D000097574:Eukaryotic Translation Initiation Factor 5A
D001119:Arginase; D008239:Lysine; D020932:Nerve Growth Factor; D010448:Peptide Initiation Factors; D011073:Polyamines; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A; C100028:hypusine