Functional significance of eIF5A and its hypusine modification in eukaryotes

Amino Acids. 2010 Feb;38(2):491-500. doi: 10.1007/s00726-009-0408-7. Epub 2009 Dec 8.

Abstract

The unusual basic amino acid, hypusine [N(epsilon)-(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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bacteria / chemistry
  • Bacteria / genetics
  • Bacteria / metabolism
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Eukaryota / chemistry
  • Eukaryota / genetics
  • Eukaryota / metabolism*
  • Fungal Proteins / chemistry
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Fungi / chemistry
  • Fungi / genetics
  • Fungi / metabolism
  • Humans
  • Lysine / analogs & derivatives*
  • Lysine / metabolism
  • Peptide Initiation Factors / chemistry
  • Peptide Initiation Factors / genetics
  • Peptide Initiation Factors / metabolism*
  • Protein Structure, Secondary
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*

Substances

  • Bacterial Proteins
  • Fungal Proteins
  • Peptide Initiation Factors
  • RNA-Binding Proteins
  • eukaryotic translation initiation factor 5A
  • hypusine
  • Lysine