Evidence map›Paper›PMID 37217939›Full record

ArticleJournal of biomedical science2023

Extracellular arginine availability modulates eIF2α O-GlcNAcylation and heme oxygenase 1 translation for cellular homeostasis.

Yu-Wen Hung, Ching Ouyang, Xiaoli Ping, Yue Qi, Yi-Chang Wang, Hsing-Jien Kung, David K Ann

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of biomedical science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.6field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Cells · 2024
    Article
  5. Review
  6. Selenomethionine Attenuated HAntioxidants (Basel, Switzerland) · 2023
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Yu-Wen HungDepartment of Diabetes Complications and Metabolism, Arthur Riggs Diabetes & Metabolism Research Institute, Beckman Research Institute of City of Hope, City of Hope Comprehensive Cancer Center, Duarte, CA, 91010-3000, USA.
Ching OuyangDepartment of Computational and Quantitative Medicine, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA.
Xiaoli PingDepartment of Diabetes Complications and Metabolism, Arthur Riggs Diabetes & Metabolism Research Institute, Beckman Research Institute of City of Hope, City of Hope Comprehensive Cancer Center, Duarte, CA, 91010-3000, USA.
Yue QiDepartment of Diabetes Complications and Metabolism, Arthur Riggs Diabetes & Metabolism Research Institute, Beckman Research Institute of City of Hope, City of Hope Comprehensive Cancer Center, Duarte, CA, 91010-3000, USA.
Yi-Chang WangDepartment of Diabetes Complications and Metabolism, Arthur Riggs Diabetes & Metabolism Research Institute, Beckman Research Institute of City of Hope, City of Hope Comprehensive Cancer Center, Duarte, CA, 91010-3000, USA.
Hsing-Jien KungCancer Center, School of Medicine, University of California, Davis, CA, 95817, USA.
David K AnnDepartment of Diabetes Complications and Metabolism, Arthur Riggs Diabetes & Metabolism Research Institute, Beckman Research Institute of City of Hope, City of Hope Comprehensive Cancer Center, Duarte, CA, 91010-3000, USA. dann@coh.org.ORCID http://orcid.org/0000-0001-6229-4241
City of Hope · USUniversity of California, Davis · US

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI John Charles Williams · 1985 to 2026
$86.3M
Epigenetic damage in women living in LA food-desert zip codesR01CA220693 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI ANN, DAVID K., HYSLOP, TERRY · 2017 to 2021
$3.7M
Fatty acids and their receptors-mediated tumor metastasis and progressionR01CA247368 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI ANN, DAVID K., YU, HUA E · 2020 to 2024
$2.0M
NCI NIH HHS P30 CA033572NCI NIH HHS R01 CA220693NCI NIH HHS R01 CA247368NIH HHS CA220693NIH HHS CA247368NIH HHS P30CA033572
6 · The paper itself

Abstract

backgroundNutrient limitations often lead to metabolic stress during cancer initiation and progression. To combat this stress, the enzyme heme oxygenase 1 (HMOX1, commonly known as HO-1) is thought to play a key role as an antioxidant. However, there is a discrepancy between the level of HO-1 mRNA and its protein, particularly in cells under stress. O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). The mechanism by which eIF2α O-GlcNAcylation regulates translation of HO-1 during extracellular arginine shortage (ArgS) remains unclear.

methodsWe used mass spectrometry to study the relationship between O-GlcNAcylation and Arg availability in breast cancer BT-549 cells. We validated eIF2α O-GlcNAcylation through site-specific mutagenesis and azido sugar N-azidoacetylglucosamine-tetraacylated labeling. We then evaluated the effect of eIF2α O-GlcNAcylation on cell recovery, migration, accumulation of reactive oxygen species (ROS), and metabolic labeling during protein synthesis under different Arg conditions.

resultsOur research identified eIF2α, eIF2β, and eIF2γ, as key O-GlcNAcylation targets in the absence of Arg. We found that O-GlcNAcylation of eIF2α plays a crucial role in regulating antioxidant defense by suppressing the translation of the enzyme HO-1 during Arg limitation. Our study showed that O-GlcNAcylation of eIF2α at specific sites suppresses HO-1 translation despite high levels of HMOX1 transcription. We also found that eliminating eIF2α O-GlcNAcylation through site-specific mutagenesis improves cell recovery, migration, and reduces ROS accumulation by restoring HO-1 translation. However, the level of the metabolic stress effector ATF4 is not affected by eIF2α O-GlcNAcylation under these conditions.

conclusionsOverall, this study provides new insights into how ArgS fine-tunes the control of translation initiation and antioxidant defense through eIF2α O-GlcNAcylation, which has potential biological and clinical implications.

Indexed as

ArginineEukaryotic Initiation Factor-2Heme Oxygenase-1AntioxidantsHomeostasisHumansReactive Oxygen SpeciesAntioxidantsArginineEukaryotic Initiation Factor-2Heme Oxygenase-1Reactive Oxygen SpeciesAntioxidant defenseArginineEukaryotic initiation factor 2αHeme oxygenase 1O-GlcNAcylationProtein translation

Identifiers

PMID37217939
PMCPMC10201738
OpenAlexW4377294115

What Socratic holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.