Dph3, a small protein required for diphthamide biosynthesis, is essential in mouse development.

Molecular and Cellular Biology
Shihui LiuStephen H Leppla

Abstract

The translation elongation factor 2 in eukaryotes (eEF-2) contains a unique posttranslationally modified histidine residue, termed diphthamide, which serves as the only target for diphtheria toxin and Pseudomonas aeruginosa exotoxin A. Diphthamide biosynthesis is carried out by five highly conserved proteins, Dph1 to Dph5, and an as-yet-unidentified amidating enzyme. The evolutionary conservation of the complex diphthamide biosynthesis pathway throughout eukaryotes implies a key role for diphthamide in normal cellular physiology. Of the proteins required for diphthamide synthesis, Dph3 is the smallest, containing only 82 residues. In addition to having a role in diphthamide biosynthesis, Dph3 is also involved in modulating the functions of the Elongator complex in yeast. To explore the physiological roles of Dph3 and to begin to investigate the function of diphthamide, we generated dph3 knockout mice and showed that dph3+/- mice are phenotypically normal, whereas dph3-/- mice, which lack the diphthamide modification on eEF-2, are embryonic lethal. Loss of both dph3 alleles causes a general delay in embryonic development accompanied by lack of allantois fusion to the chorion and increased degeneration and necrosis in neural tube...Continue Reading

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Citations

Apr 18, 2012·Proceedings of the National Academy of Sciences of the United States of America·Hui WeiIra Pastan
Aug 8, 2012·Proceedings of the National Academy of Sciences of the United States of America·Shihui LiuStephen H Leppla
Jul 4, 2012·Cold Spring Harbor Perspectives in Biology·Thomas E Dever, Rachel Green
Dec 6, 2006·Molecular and Cellular Biology·Jeffrey M C LauAnthony J Muslin
May 7, 2013·Toxins·Wael Abdel-FattahRaffael Schaffrath
Jun 5, 2014·Human Molecular Genetics·Yi-Ru YuChun-Ming Chen
Sep 27, 2014·BMC Genetics·Priscila S N de OliveiraLuciana C A Regitano
Jul 28, 2010·Toxicon : Official Journal of the International Society on Toxinology·Ashima K Sharma, David FitzGerald
Jan 25, 2008·Proteins·Fangming WuYunyu Shi
May 8, 2008·Cellular Microbiology·Pradeep K GuptaStephen H Leppla
Jun 1, 2011·The FEBS Journal·Eva GreganovaPeter Bütikofer
Oct 30, 2014·Molecular Microbiology·Raffael SchaffrathMichael J R Stark
Aug 12, 2015·Proceedings of the National Academy of Sciences of the United States of America·Sebastian StahlUlrich Brinkmann
Aug 27, 2013·Critical Reviews in Biochemistry and Molecular Biology·Xiaoyang SuHening Lin
Aug 16, 2016·Journal of Chemical Information and Modeling·Jean-Marc BillodLeif A Eriksson
Nov 22, 2012·Proceedings of the National Academy of Sciences of the United States of America·Xiaoyang SuHening Lin
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May 16, 2020·Scientific Reports·Maria Giovanna MaturoRajiv Kumar
Sep 12, 2021·Proceedings of the National Academy of Sciences of the United States of America·Yugang ZhangHening Lin

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