ArticleRedox biology2019
Diphthamide affects selenoprotein expression: Diphthamide deficiency reduces selenocysteine incorporation, decreases selenite sensitivity and pre-disposes to oxidative stress.
Article in Redox biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 30 citations in OpenAlex.
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- Altered transposon element-derived genes distort oxygen-free radical scavenger systems in FXD.NAR molecular medicine · 2026Article
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- Diphthamide synthesis is linked to the eEF2-client chaperone machinery.FEBS letters · 2025Article
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- Mild sleep restriction increases endothelial oxidative stress in female persons.Scientific reports · 2023Article
- DPH1 and DPH2 variants that confer susceptibility to diphthamide deficiency syndrome in human cells and yeast models.Disease models & mechanisms · 2023Article
- Iron in Translation: From the Beginning to the End.Microorganisms · 2021Review
- Inhibition of selenoprotein synthesis by Zika virus may contribute to congenital Zika syndrome and microcephaly by mimicking SELENOP knockout and the genetic disease PCCA.BBA advances · 2021Article
- Diphthamide-deficiency syndrome: a novel human developmental disorder and ribosomopathy.European journal of human genetics : EJHG · 2020Article
- Identification of the transcription factor Miz1 as an essential regulator of diphthamide biosynthesis using a CRISPR-mediated genome-wide screen.PLoS genetics · 2020Article
- Mechanisms of Resistance to Immunotoxins ContainingBiomolecules · 2020Review
- Forward genetic screen in human podocytes identifies diphthamide biosynthesis genes as regulators of adhesion.American journal of physiology. Renal physiology · 2019Article
- The Crystal Structure of Dph2 in Complex with Elongation Factor 2 Reveals the Structural Basis for the First Step of Diphthamide Biosynthesis.Biochemistry · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
The diphthamide modification of translation elongation factor 2 is highly conserved in eukaryotes and archaebacteria. Nevertheless, cells lacking diphthamide can carry out protein synthesis and are viable. We have analyzed the phenotypes of diphthamide deficient cells and found that diphthamide deficiency reduces selenocysteine incorporation into selenoproteins. Additional phenotypes resulting from diphthamide deficiency include altered tRNA-synthetase and selenoprotein transcript levels, hypersensitivity to oxidative stress and increased selenite tolerance. Diphthamide-eEF2 occupies the aminoacyl-tRNA translocation site at which UGA either stalls translation or decodes selenocysteine. Its position is in close proximity and mutually exclusive to the ribosomal binding site of release/recycling factor ABCE1, which harbors a redox-sensitive Fe-S cluster and, like diphthamide, is present in eukaryotes and archaea but not in eubacteria. Involvement of diphthamide in UGA-SECIS decoding may explain deregulated selenoprotein expression and as a consequence oxidative stress, NFkB activation and selenite tolerance in diphthamide deficient cells.
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Registered trials
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