Evidence map›Paper›PMID 23027940›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2012

Modification of RelA by O-linked N-acetylglucosamine links glucose metabolism to NF-κB acetylation and transcription.

David F Allison, J Jacob Wamsley, Manish Kumar, Duo Li, Lisa G Gray, Gerald W Hart, David R Jones, Marty W Mayo

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

76 citing papers in PubMed, 126 citations in OpenAlex.

  1. Review
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  6. Frontiers in immunology · 2025
    Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Post-translational modifications of p65: state of the art.Frontiers in cell and developmental biology · 2024
    Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Review
  20. Article

16 more citing papers are in PubMed but not listed here.

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

8 authors at 2 institutions in 1 country.

David F AllisonDepartment of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA.
J Jacob Wamsley
Manish Kumar
Duo Li
Lisa G Gray
Gerald W Hart
David R Jones
Marty W Mayo
Johns Hopkins University · USUniversity of Virginia · US

Funding

Shared Resource CoresP01HL107153 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI HART, GERALD WARREN · 2011 to 2017
$16.8M
TRAINING IN CELL AND MOLECULAR BIOLOGYT32GM008136 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI STUKENBERG, P. TODD · 1985 to 2020
$8.5M
Cytosolic O-Glycosylation and Insulin SignalingR01DK061671 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI HART, GERALD WARREN · 2002 to 2014
$4.0M
Role of IKK in NSCLC: Modulation of SMRT and NF-kappaBR01CA104397 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI MAYO, MARTY W · 2004 to 2012
$2.4M
Epigenetic and post-translational regulation of the metastasis suppressor BRMS1R01CA136705 · NCI · UNIVERSITY OF VIRGINIA · PI JONES, DAVID R · 2009 to 2013
$1.5M
Inflammatory Cytokines Link NF-kappaB with Bim Degradation and MetastasisR01CA132580 · NCI · UNIVERSITY OF VIRGINIA · PI MAYO, MARTY W · 2008 to 2012
$1.4M
NCI NIH HHS R01 CA104397NCI NIH HHS R01CA104397NCI NIH HHS R01 CA132580NCI NIH HHS R01CA132580NCI NIH HHS R01 CA136705NCI NIH HHS R01CA136705NHLBI NIH HHS P01 HL107153NHLBI NIH HHS P01HL107153NIDDK NIH HHS R01 DK061671NIDDK NIH HHS R01DK61671NIGMS NIH HHS T32 GM008136
6 · The paper itself

Abstract

The molecular mechanisms linking glucose metabolism with active transcription remain undercharacterized in mammalian cells. Using nuclear factor-κB (NF-κB) as a glucose-responsive transcription factor, we show that cells use the hexosamine biosynthesis pathway and O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) to potentiate gene expression in response to tumor necrosis factor (TNF) or etoposide. Chromatin immunoprecipitation assays demonstrate that, upon induction, OGT localizes to NF-κB-regulated promoters to enhance RelA acetylation. Knockdown of OGT abolishes p300-mediated acetylation of RelA on K310, a posttranslational mark required for full NF-κB transcription. Mapping studies reveal T305 as an important residue required for attachment of the O-GlcNAc moiety on RelA. Furthermore, p300 fails to acetylate a full-length RelA(T305A) mutant, linking O-GlcNAc and acetylation events on NF-κB. Reconstitution of RelA null cells with the RelA(T305A) mutant illustrates the importance of this residue for NF-κB-dependent gene expression and cell survival. Our work provides evidence for a unique regulation where attachment of the O-GlcNAc moiety to RelA potentiates p300 acetylation and NF-κB transcription.

Indexed as

AcetylationAcetylglucosamineChromatin ImmunoprecipitationDNA, ComplementaryEnzyme-Linked Immunosorbent AssayEtoposideGene Expression RegulationGlucoseHEK293 CellsHexosaminesHumansImmunoblottingImmunoprecipitationLuciferasesMetabolic Networks and PathwaysNF-kappa BAcetylglucosamineDNA, ComplementaryEtoposideGlucoseHexosaminesLuciferasesNF-kappa BRELA protein, humanTranscription Factor RelATumor Necrosis Factor-alpha

Identifiers

PMID23027940
PMCPMC3479489
OpenAlexW2146191481

What OpenQuestion holds

Textmetadata
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.