Hypusine biosynthesis in protein and its biological consequences.

Abstract

In 1971, the amino acid known as hypusine was discovered in free form in bovine brain (Shiba et al., 1972). The structure of hypusine was established and confirmed as N6-(4-amino-2-hydroxybutyl)-2, 6-diamino hexanoic acid (Shiba et al., 1982; Tice and Ganem, 1983). Since its discovery, hypusine has been found as a free amino acid (Nakajima et al., 1971) and bound to protein (Sano et al., 1984). Protein-bound hypusine primarily occurred in a protein, M ≃ 18, 000, which was originally observed in lectin-stimulated lymphocytes and Chinese hamster ovary (CHO) cells (Park et al., 1981; Cooper et al, 1982). The synthesis of protein-bound hypusine coincides with an increase in protein synthesis (Cooper et al., 1982) and this biochemical process was observed in several mammalian cell lines (Chen, 1983; Torrelio et al., 1984). Because of the ubiquity of the hypusine modification in an Mr ≃ 18, 000 protein and its conservation among eukaryotes (Paric et al., 1984a; Gordon et al., 1987), the biophysical characteristics of the protein were compared to those of known eukaryotic protein translation initiation factors. The MΓ ≃ 18, 000 protein modified by hypusine was identified as the putative eukaryotic protein synthesis initiation factor eIF-4D (Cooper et al., 1983).