EFFECT OF INITIATION FACTOR eIF-5A DEPLETION ON CELL PROLIFERATION AND PROTEIN SYNTHESIS

Initiation factor eIF-5A (formerly called eIF-4D) was originally isolated (Kemper et al., 1976; Benne et al., 1978) from rabbit reticulocytes based on its activity in stimulating the synthesis of methionyl-puromycin, a model of the formation of the first peptide bond in protein synthesis. This highly conserved protein is small (ca. 18 kDa) and acidic (pI = 5.4) and is one of the most abundant initiation factors in mammalian cells. eIF-5A is unique in undergoing a covalent post-translational modification by a two-step pathway that involves the attachment of an aminobutyl group from spermidine to the e-amino group of a lysine residue, followed by hydroxylation on the number 2 carbon of the butyl group, to form a hypusine residue (Park et al., 1984). The hypusination reaction correlates with stimulation of cell growth and protein synthesis, thereby eliciting considerable interest in the protein.