Talk:Diphthamide

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It is usually found at position H715 in mammalian eEF2 (H699 in yeast). This residue is modified by the protein encoded by the [[DPH1|DPH1 (OVCA1)]] gene. Dph1 [[knockout mice]] are inviable while [[heterozygote]]s develop diverse types of [[carcinoma]]s and [[sarcoma]]s. In humans, DH1 is frequently found mutated in [[ovarian cancer]]. [[Loss of heterozygosity]] has taken place in 50% of benign tumours, and 90% of end-stage ovarian tumours. It is an [[ADP ribosylation|ADP-ribosylated]]{{clarify|"ADP-ribosylated" is an adjective. What noun is it modifying?|date=December 2015}} by [[diphtheria toxin]], hence the name, which renders the elongation factor inactive. [[Nicotinamide adenine dinucleotide]] (NAD) serves as its ADP-ribosyl donor.<ref>{{Cite journal|url = |title = Understanding the mode of action of diphtheria toxin: a perspective on progress during the 20th century.|last = Collier|first = R.J.|date = 2001|journal = Toxicon|doi = 10.1016/S0041-0101(01)00165-9|pmid = 11595641|volume=39|pages=1793–803}}</ref> The inactivation of the elongation factor results in a halt in protein synthesis, which in turn leads to cell death.<ref>{{Cite journal|url = |title = Diphtheria toxin-dependent adenosine diphosphate ribosylation of aminoacyl transferase II and inhibition of protein synthesis|last = Honjo|first = T|date = 1968|journal = J. Biol. Chem.|doi = |pmid = 4297784|volume=243|pages=3553–5}}</ref><ref name=":0">{{Cite journal|url = |title = The life and death of translation elongation factor 2.|last = Jorgensen|first = R|date = 2006|journal = Biochem Soc Trans|doi = 10.1042/BST20060001|pmid = 16246167|volume=34|pages=1–6}}</ref> Diphthamide consists of seven genes namely DH1, DH2, DH3, DH4, DH5, DH6, and DH7.{{clarify|It doesn't make any sense to say a chemical compound consists of several genes|date=December 2015}} According to research conducted by Sebastian Stahl et al., the loss of diphthamide or presence of unmodified eEF2 does not severely impact cell growth under normal conditions. However, animals with homozygous DPHko do not survive beyond embryonic stages, suggesting that the diphthamide may be necessary for development.<ref name=":1">{{Cite journal|pmc = 4553792|title = Loss of diphthamide pre-activates NF-κB and death receptor pathways and renders MCF7 cells hypersensitive to tumor necrosis factor|last = Stahl|first = Sebastian|date = 2015|journal = Proc Natl Acad Sci U S A|doi = 10.1073/pnas.1512863112|pmid = 26261303|volume=112|pages=10732–7}}</ref>