Identification of the Proteins Required for Biosynthesis of Diphthamide, the Target of Bacterial ADP-Ribosylating Toxins on Translation Elongation Factor 2

• DOI: 10.1128/mcb.24.21.9487-9497.2004
• Publication Date: 2004-10-14T00:38:32Z
• Authors: Shihui Liu; G. Todd Milne; Jeffrey G. Kuremsky; Gerald R. Fink; Stephen H. Leppla
• Keywords: Elongation factor; Diphtheria Toxin

Diphthamide, a posttranslational modification of translation elongation factor 2 that is conserved in all eukaryotes and archaebacteria the target diphtheria toxin, formed yeast by actions five proteins, Dph1 to -5, still unidentified amidating enzyme.Dph2 Dph5 were previously identified.Here, we report identification remaining three proteins ( Dph1, -3, and-4) show Dph have either functional -2, and-5) or sequence (Dph4) homologs mammals.We propose unified nomenclature for these (e.g., HsDph1 -5 human proteins) their genes based on nomenclature.We Dph2 are homologous but functionally independent.The tumor suppressor gene OVCA1, identified as DPH2, shown actually be HsDPH1.We HsDPH3 described toxin Pseudomonas exotoxin A sensitivity required 1 DPH4 encodes CSL zinc finger-containing DnaJ-like protein.Other features also discussed.The physiological function diphthamide basis its ubiquity remain mystery, evidence presented -3 vivo protein complex multiple cellular processes.