The role of mammalian initiation factor eIF-4D and its hypusine modification in translation.
Initiation factor eIF-4D functions late in the initiation pathway, apparently during formation of the first peptide bond. The factor is post-translationally modified at a specific lysine residue by reaction with spermidine and subsequent hydroxylation to form hypusine. A precursor form lacking hypusine is inactive in the assay for methionyl-puromycin synthesis, but activity is restored following in vitro modification to deoxyhypusine, thereby suggesting that the modification is essential for function. Since formylated methionyl-tRNA is less dependent on eIF-4D in the puromycin assay, we postulate that eIF-4D and its hypusine modification may stabilize charged Met-tRNA binding to the peptidyl transferase center of the 60S ribosomal subunit. Analysis of eIF-4D genes in yeast indicate that eIF-4D and its hypusine modification are essential for cell growth.
Hershey
J W
JW
Department of Biological Chemistry, School of Medicine, University of California, Davis 95616.
Smit-McBride
Z
Z
Schnier
J
J
D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008239:Lysine / Q000031:analogs & derivatives*; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D011691:Puromycin / Q000031:analogs & derivatives / Q000096:biosynthesis; D012358:RNA, Transfer, Met / Q000378:metabolism; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A
D008239:Lysine; D010448:Peptide Initiation Factors; D011691:Puromycin; D012358:RNA, Transfer, Met; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A; C100028:hypusine; C024777:methionylpuromycin