Diphthamide affects selenoprotein expression: Diphthamide deficiency reduces selenocysteine incorporation, decreases selenite sensitivity and pre-disposes to oxidative stress.
Amino Acyl-tRNA Synthetases
/ genetics
Cell Line, Tumor
Gene Expression Regulation
/ drug effects
Histidine
/ analogs & derivatives
Humans
NF-kappa B
/ metabolism
Oxidative Stress
/ drug effects
Reactive Oxygen Species
/ metabolism
Selenious Acid
/ pharmacology
Selenocysteine
/ metabolism
Selenoproteins
/ genetics
Diphtheria toxin
Eukaryotic translation elongation factor 2
Oxidative stress
Selenocysteine
Journal
Redox biology
ISSN: 2213-2317
Titre abrégé: Redox Biol
Pays: Netherlands
ID NLM: 101605639
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
06
06
2018
revised:
17
09
2018
accepted:
24
09
2018
pubmed:
13
10
2018
medline:
2
4
2019
entrez:
13
10
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30312900
pii: S2213-2317(18)30485-3
doi: 10.1016/j.redox.2018.09.015
pmc: PMC6180344
pii:
doi:
Substances chimiques
NF-kappa B
0
Reactive Oxygen Species
0
Selenoproteins
0
Selenocysteine
0CH9049VIS
Histidine
4QD397987E
diphthamide
75645-22-6
Amino Acyl-tRNA Synthetases
EC 6.1.1.-
Selenious Acid
F6A27P4Q4R
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
146-156Informations de copyright
Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
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