Hypusine formation in eukaryotic initiation factor 4D is not reversed when rates or specificity of protein synthesis is altered.
In mammalian cells, a single major cellular protein (eukaryotic initiation factor 4D) is post-translationally modified by the conversion of a lysine residue into the unusual amino acid hypusine. This modification was reported to occur during mitogen-stimulated growth of lymphocytes but not during quiescence, suggesting that alternative forms of eukaryotic initiation factor 4D might play a role in the regulation of cell growth perhaps through the control of protein synthesis itself (Cooper, H. L., Park, M. H., and Folk, J. E. (1982) Cell 29, 791-797). We took advantage of the drastic changes in translational specificity which occur in heat-shocked cells of Drosophila melanogaster, and of the wide variations in translation rates which occur in response to alterations of growth media in the fungus Saccharomyces cerevisiae, to investigate the relationship between the intracellular level and state of modification of the hypusine-containing protein and the rate and specificity of translation. We also studied whether the hypusine residue in this protein might be subject to further modification or reversion to lysine. Under all conditions examined, the protein was remarkably long-lived. Furthermore, the hypusine persists in this protein as hypusine, without further modification or reversion to lysine. Thus, we observe no correlation between the state of cellular translation and the persistence or reversal of this protein's modification. In addition, the data imply that neither are the state of such key cellular processes as DNA replication, RNA transcription, or carbohydrate metabolism so correlated.
D000818:Animals; D004331:Drosophila melanogaster / Q000378:metabolism; D005470:Fluorometry; D006358:Hot Temperature; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D010448:Peptide Initiation Factors / Q000096:biosynthesis*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013172:Spores, Fungal; D000097574:Eukaryotic Translation Initiation Factor 5A
D008239:Lysine; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A; C100028:hypusine