Evidence map›Paper›PMID 27466442›Full record

ArticleOpen biology2016

Dynamic phosphorylation of RelA on Ser42 and Ser45 in response to TNFα stimulation regulates DNA binding and transcription.

Francesco Lanucara, Connie Lam, Jelena Mann, Tom P Monie, Stefano A P Colombo, Stephen W Holman, James Boyd, Manohar C Dange, Derek A Mann, Michael R H White and 1 more

Open access · goldAbstract read
In one paragraph

Article in Open biology, 2016. 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
0.8field-weighted citation impact, top 28% 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, 27 citations in OpenAlex.

  1. Article
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  5. Post-translational modifications of p65: state of the art.Frontiers in cell and developmental biology · 2024
    Review
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  12. Review
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  15. NF-κB p65 dimerization and DNA-binding is important for inflammatory gene expression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
  16. Article
  17. 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

11 authors at 4 institutions in 1 country.

Francesco LanucaraCentre for Proteome Research, Department of Biochemistry, Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK.
Connie LamSystems Microscopy Centre, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
Jelena MannFibrosis Laboratory, Liver Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Tom P MonieMRC Human Nutrition Research, University of Cambridge, Cambridge CB2 1GA, UK.
Stefano A P ColomboSystems Microscopy Centre, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
Stephen W HolmanCentre for Proteome Research, Department of Biochemistry, Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK.
James BoydSystems Microscopy Centre, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
Manohar C DangeCentre for Proteome Research, Department of Biochemistry, Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK.
Derek A MannFibrosis Laboratory, Liver Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Michael R H WhiteSystems Microscopy Centre, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
Claire E EyersCentre for Proteome Research, Department of Biochemistry, Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK claire.eyers@liverpool.ac.uk.ORCID 0000-0002-3223-5926
University of Liverpool · GBUniversity of Manchester · GBNewcastle University · GBMRC Human Nutrition Research · GB

Funding

Biotechnology and Biological Sciences Research Council BB/E024181/1Biotechnology and Biological Sciences Research Council BB/F00561X/1Biotechnology and Biological Sciences Research Council BB/F005938/1Biotechnology and Biological Sciences Research Council BB/F005938/2Biotechnology and Biological Sciences Research Council BB/G009058/1Biotechnology and Biological Sciences Research Council BB/K003097/1Biotechnology and Biological Sciences Research Council BB/L009501/1Medical Research Council MC_U105960399Medical Research Council MR/K001949/1Wellcome Trust WT0805090MA
6 · The paper itself

Abstract

The NF-κB signalling module controls transcription through a network of protein kinases such as the IKKs, as well as inhibitory proteins (IκBs) and transcription factors including RelA/p65. Phosphorylation of the NF-κB subunits is critical for dictating system dynamics. Using both non-targeted discovery and quantitative selected reaction monitoring-targeted proteomics, we show that the cytokine TNFα induces dynamic multisite phosphorylation of RelA at a number of previously unidentified residues. Putative roles for many of these phosphorylation sites on RelA were predicted by modelling of various crystal structures. Stoichiometry of phosphorylation determination of Ser45 and Ser42 revealed preferential early phosphorylation of Ser45 in response to TNFα. Quantitative analyses subsequently confirmed differential roles for pSer42 and pSer45 in promoter-specific DNA binding and a role for both of these phosphosites in regulating transcription from the IL-6 promoter. These temporal dynamics suggest that RelA-mediated transcription is likely to be controlled by functionally distinct NF-κB proteoforms carrying different combinations of modifications, rather than a simple 'one modification, one effect' system.

Indexed as

Cell LineCrystallography, X-RayDNAGene Expression RegulationHumansInterleukin-6Models, MolecularPhosphorylationPromoter Regions, GeneticProtein BindingProtein ConformationProteomicsSerineTranscription Factor RelATranscription, GeneticTumor Necrosis Factor-alphaDNAIL6 protein, humanInterleukin-6RELA protein, humanSerineTNF protein, humanTranscription Factor RelATumor Necrosis Factor-alphaNF-κBphosphorylationproteomicsquantificationRelAtranscription

Identifiers

PMID27466442
PMCPMC4967822
OpenAlexW2500053863

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.