Loss of Diphthamide Pre-Activates NF-κB and Death Receptor Pathways and Renders MCF7 Cells Hypersensitive to Tumor Necrosis Factor

SignificanceDiphthamide is a conserved modification on eukaryotic translation elongation factor 2 (eEF2). Analyses of genetically defined diphthamide-deficient cell lines indicate that this modification determines not only sensitivity of cells to the ADP-ribosylating toxinsPseudomonasexotoxin A and diphtheria toxin, but it also modulates nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) and TNF receptor signaling pathways.