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Functional significance of eIF5A and its hypusine modification in eukaryotes
Open accessAbstract
The unusual basic amino acid, hypusine [Nε-(4-amino-2-hydroxybutyl)-lysine], is a modified lysine with the addition of the 4-aminobutyl moiety from the polyamine spermidine. This naturally occurring amino acid is a product of a unique posttranslational modification that occurs in only one cellular protein, eukaryotic translation initiation factor 5A (eIF5A, eIF-5A). Hypusine is synthesized exclusively in this protein by two sequential enzymatic steps involving deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH). The deoxyhypusine/hypusine synthetic pathway has evolved in archaea and eukaryotes, and eIF5A, DHS and DOHH are highly conserved suggesting a vital cellular function of eIF5A. Gene disruption and mutation studies in yeast and higher eukaryotes have provided valuable information on the essential nature of eIF5A and the deoxyhypusine/hypusine modification in cell growth and in protein synthesis. In view of the extraordinary specificity and functional significance of hypusine-containing eIF5A in mammalian cell proliferation, eIF5A and the hypusine biosynthetic enzymes are novel potential targets for intervention in aberrant cell proliferation.
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Cited by
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Casero, R. A., Murray Stewart, T., & Pegg, A. E. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0050-3 · Cited by 817
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Miller-Fleming, L., Olin-Sandoval, V., Campbell, K., & Ralser, M. (2015) · Journal of Molecular Biology · doi:10.1016/j.jmb.2015.06.020 · Cited by 658
eIF5A Promotes Translation of Polyproline Motifs
Gutierrez, E., Shin, B.-S., Woolstenhulme, C. J., Kim, J.-R., Saini, P., Buskirk, A. R., & Dever, T. E. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.04.021 · Cited by 522
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Metadata
- Authors
- Park, M. H., Nishimura, K., Zanelli, C. F., & Valentini, S. R.
- Venue
- Amino Acids
- Published
- 2009-12-08
- Volume
- 38
- Issue
- 2
- Pages
- 491-500
- ISSN
- 0939-4451 (ISSN-L)
- 1438-2199
- OpenAlex
- W2083119952
- Cited by
- 343
- References
- 0
- FWCI
- 5.88
- Type
- journal article
- Language
- en
- Open access
- green
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- Park, M. H., Nishimura, K., Zanelli, C. F., & Valentini, S. R. (2010). Functional significance of eIF5A and its hypusine modification in eukaryotes. Amino Acids. https://doi.org/10.1007/s00726-009-0408-7
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