Evidence map›Paper›PMID 34997181›Full record

ArticleLeukemia2022

MYC, mitochondrial metabolism and O-GlcNAcylation converge to modulate the activity and subcellular localization of DNA and RNA demethylases.

An-Ping Lin, Zhijun Qiu, Purushoth Ethiraj, Binu Sasi, Carine Jaafar, Dinesh Rakheja, Ricardo C T Aguiar

Open access · greenAbstract read
In one paragraph

Article in Leukemia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

17 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Article
  3. Dual-action peptide KWHVeterinary research · 2026
    Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. TET1 overexpression affects cell proliferation and apoptosis in aging ovaries.Journal of assisted reproduction and genetics · 2024
    Article
  12. Dynamic multilayered control of mProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  13. TET3-overexpressing macrophages promote endometriosis.The Journal of clinical investigation · 2024
    Article
  14. Article
  15. Review
  16. Article
  17. Review
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.

An-Ping Lin *Division of Hematology and Medical Oncology, Department of Medicine, University of Texas Health Science Center San Antonio, San Antonio, TX, 78229, USA.
Zhijun Qiu *Division of Hematology and Medical Oncology, Department of Medicine, University of Texas Health Science Center San Antonio, San Antonio, TX, 78229, USA.
Purushoth EthirajDivision of Hematology and Medical Oncology, Department of Medicine, University of Texas Health Science Center San Antonio, San Antonio, TX, 78229, USA.ORCID http://orcid.org/0000-0002-0679-6041
Binu SasiDivision of Hematology and Medical Oncology, Department of Medicine, University of Texas Health Science Center San Antonio, San Antonio, TX, 78229, USA.ORCID http://orcid.org/0000-0002-3325-9874
Carine JaafarDivision of Hematology and Medical Oncology, Department of Medicine, University of Texas Health Science Center San Antonio, San Antonio, TX, 78229, USA.
Dinesh RakhejaDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.ORCID http://orcid.org/0000-0001-6888-7902
Ricardo C T AguiarDivision of Hematology and Medical Oncology, Department of Medicine, University of Texas Health Science Center San Antonio, San Antonio, TX, 78229, USA. aguiarr@uthscsa.edu.ORCID http://orcid.org/0000-0002-8791-5849
The University of Texas Health Science Center at San Antonio · USThe University of Texas Southwestern Medical Center · US

Funding

Oxidative stress and RNA methylationR01ES031522 · NIEHS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI AGUIAR, RICARDO C · 2020 to 2024
$1.9M
Mitochondrial 2-hydroxyglutarate dehydrogenases modulate the cellular epitranscriptomeR01GM140456 · NIGMS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI AGUIAR, RICARDO C · 2021 to 2024
$1.2M
Post-Translational Control of TET Function in LymphomaI01BX001882 · VA · SOUTH TEXAS VETERANS HEALTH CARE SYSTEM · PI AGUIAR, RICARDO C · 2013 to 2025
–
BLRD VA I01 BX001882NIEHS NIH HHS R01 ES031522NIGMS NIH HHS R01 GM140456
6 · The paper itself

Abstract

Mitochondria can function as signaling organelles, and part of this output leads to epigenetic remodeling. The full extent of this far-reaching interplay remains undefined. Here, we show that MYC transcriptionally activates IDH2 and increases alpha-ketoglutarate (αKG) levels. This regulatory step induces the activity of αKG-dependent DNA hydroxylases and RNA demethylases, thus reducing global DNA and RNA methylation. MYC, in a IDH2-dependent manner, also promotes the nuclear accumulation of TET1-TET2-TET3, FTO and ALKBH5. Notably, this subcellular movement correlated with the ability of MYC, in an IDH2-dependent manner, and, unexpectedly, of αKG to directly induce O-GlcNAcylation. Concordantly, modulation of the activity of OGT and OGA, enzymes that control the cycling of this non-canonical mono-glycosylation, largely recapitulated the effects of the MYC-IDH2-αKG axis on the subcellular movement of DNA and RNA demethylases. Together, we uncovered a hitherto unsuspected crosstalk between MYC, αKG and O-GlcNAcylation which could influence the epigenome and epitranscriptome homeostasis.

Indexed as

DNA MethylationRNAAlpha-Ketoglutarate-Dependent Dioxygenase FTODNADNA-Binding ProteinsHumansMitochondriaMixed Function OxygenasesProto-Oncogene ProteinsAlpha-Ketoglutarate-Dependent Dioxygenase FTODNADNA-Binding ProteinsFTO protein, humanMixed Function OxygenasesProto-Oncogene ProteinsRNATET1 protein, human

Identifiers

PMID34997181
PMCPMC8983447
OpenAlexW4205347299

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.