Evidence map›Paper›PMID 26989780›Full record

ArticleScience advances2016

Citrullination-acetylation interplay guides E2F-1 activity during the inflammatory response.

Fatemeh Ghari, Anne-Marie Quirke, Shonagh Munro, Joanna Kawalkowska, Sarah Picaud, Joanna McGouran, Venkataraman Subramanian, Aaron Muth, Richard Williams, Benedikt Kessler and 5 more

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

Article in Science advances, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 1 pooled it
5.7field-weighted citation impact, top 4% 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

53 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. NAR genomics and bioinformatics · 2024
    Article
  11. Citrullination and the protein code: crosstalk between post-translational modifications in cancer.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Review
  12. Transcriptomic analysis of PADI4 target genes during multi-lineage differentiation of embryonic stem cells.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Article
  13. Protein citrullination: inhibition, identification and insertion.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Review
  14. Development of LB244, an Irreversible STING Antagonist.Journal of the American Chemical Society · 2023
    Article
  15. Targeting STING oligomerization with small-molecule inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  16. Article
  17. Review
  18. The virtues and vices of protein citrullination.Royal Society open science · 2022
    Review
  19. Dihydroartemisinin ameliorates chronic nonbacterial prostatitis and epithelial cellular inflammation by blocking the E2F7/HIF1α pathway.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022
    Article
  20. 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

15 authors at 4 institutions in 2 countries.

Fatemeh GhariDepartment of Oncology, University of Oxford, Oxford OX3 7DQ, UK.
Anne-Marie QuirkeKennedy Institute, University of Oxford, Oxford OX3 7DQ, UK.ORCID 0000-0003-2335-1631
Shonagh MunroDepartment of Oncology, University of Oxford, Oxford OX3 7DQ, UK.
Joanna KawalkowskaKennedy Institute, University of Oxford, Oxford OX3 7DQ, UK.ORCID 0000-0003-2581-8397
Sarah PicaudStructural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK.
Joanna McGouranUniversity of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Venkataraman SubramanianLudwig Institute, University of Oxford, Oxford OX3 7DQ, UK.
Aaron MuthLudwig Institute, University of Oxford, Oxford OX3 7DQ, UK.ORCID 0000-0002-6178-7682
Richard WilliamsKennedy Institute, University of Oxford, Oxford OX3 7DQ, UK.ORCID 0000-0001-5473-5270
Benedikt KesslerUniversity of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Paul R ThompsonLudwig Institute, University of Oxford, Oxford OX3 7DQ, UK.
Panagis FillipakopoulosStructural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK.; Target Discovery Institute, University of Oxford, Oxford OX3 7DQ, UK.
Stefan KnappStructural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK.ORCID 0000-0002-0604-9185
Patrick J VenablesKennedy Institute, University of Oxford, Oxford OX3 7DQ, UK.
Nicholas B La ThangueDepartment of Oncology, University of Oxford, Oxford OX3 7DQ, UK.
University of Oxford · GBCRUK/MRC Oxford Institute for Radiation Oncology · GBLudwig Cancer Research · GBUniversity of Massachusetts Chan Medical School · US

Funding

Haloacetamidine based inactivators of Protein Arginine Deiminase 4R01GM079357 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI THOMPSON, PAUL R · 2007 to 2016
$3.3M
Cancer Research UK 13058Cancer Research UK 20776Medical Research Council G0500905Medical Research Council G1000807Medical Research Council G9400953NIADDK NIH HHS AM110394NIGMS NIH HHS R01 GM079357Wellcome TrustWellcome Trust 097813/Z/11/Z
6 · The paper itself

Abstract

Peptidyl arginine deiminase 4 (PAD4) is a nuclear enzyme that converts arginine residues to citrulline. Although increasingly implicated in inflammatory disease and cancer, the mechanism of action of PAD4 and its functionally relevant pathways remains unclear. E2F transcription factors are a family of master regulators that coordinate gene expression during cellular proliferation and diverse cell fates. We show that E2F-1 is citrullinated by PAD4 in inflammatory cells. Citrullination of E2F-1 assists its chromatin association, specifically to cytokine genes in granulocyte cells. Mechanistically, citrullination augments binding of the BET (bromodomain and extra-terminal domain) family bromodomain reader BRD4 (bromodomain-containing protein 4) to an acetylated domain in E2F-1, and PAD4 and BRD4 coexist with E2F-1 on cytokine gene promoters. Accordingly, the combined inhibition of PAD4 and BRD4 disrupts the chromatin-bound complex and suppresses cytokine gene expression. In the murine collagen-induced arthritis model, chromatin-bound E2F-1 in inflammatory cells and consequent cytokine expression are diminished upon small-molecule inhibition of PAD4 and BRD4, and the combined treatment is clinically efficacious in preventing disease progression. Our results shed light on a new transcription-based mechanism that mediates the inflammatory effect of PAD4 and establish the interplay between citrullination and acetylation in the control of E2F-1 as a regulatory interface for driving inflammatory gene expression.

Indexed as

AcetylationAnimalsArthritis, ExperimentalBromodomain Containing ProteinsCell Cycle ProteinsCell LineCitrullineCytokinesE2F1 Transcription FactorGene Expression RegulationHL-60 CellsHumansHydrolasesInflammationMaleMiceBRD4 protein, humanBromodomain Containing ProteinsCell Cycle ProteinsCitrullineCytokinesE2F1 protein, humanE2F1 Transcription FactorHydrolasesNuclear ProteinsPADI4 protein, humanpeptidylarginine deiminase 4, mouseProtein-Arginine DeiminasesProtein-Arginine Deiminase Type 4Recombinant ProteinsRNA, Small InterferingTranscription FactorsBRD4cancercitrullinationE2F-1immune responseinflammationPAD4

Identifiers

PMID26989780
PMCPMC4788482
OpenAlexW2270324339

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.